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  • bioavailability
  • Springer  (35)
  • Annual Reviews
  • Blackwell Publishing Ltd
  • 2005-2009
  • 1990-1994  (35)
  • 1980-1984
  • 1975-1979
  • 1993  (35)
Collection
Keywords
Publisher
  • Springer  (35)
  • Annual Reviews
  • Blackwell Publishing Ltd
Years
  • 2005-2009
  • 1990-1994  (35)
  • 1980-1984
  • 1975-1979
Year
  • 1
    Electronic Resource
    Electronic Resource
    Bioverfügbarkeit von Aminosäuren aus einigen industriell gefertigten proteinhaltigen Produkten (1993)
    Springer
    European journal of nutrition 32 (1993), S. 2-20 
    Details
    ISSN: 1436-6215
    Keywords: Aminosäuren ; Proteine ; proteinhaltige Produkte, Bioverfügbarkeit, Biokinetik ; Technologie ; amino acids ; proteins ; protein-containing products ; bioavailability ; biokinetics ; technology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Summary To evaluate the bioavailability of amino acids from proteins and protein-containing products, the area under the postprandial plasma-concentration-time-curve of the amino acids after oral administration needs to be calculated. Therefore, basic values depending on circadian plasma concentration rhythms have to be subtracted from measured values after loading. To determine the relative bioavailability of two tested samples, e.g., a protein-containing product before and after processing or two technologically different preparations of the same protein, it is sufficient to compare their absorption-curves, both corrected by the basic values. For that purpose the mean value-curves corresponding to the group of subjects are used, because the individual courses show considerable differences, in particular due to discontinuous gastric emptying. Enzymatic hydrolysis of a lactalbumin reduces the quantitative bioavailability of the amino acids by 12%. Concerning products used in nutrition of patients and babies, the availability from ready-to-drink liquid products is about 7–10% better than that out of the same dry products in powdered form. Compared with sterilization, ultrahigh heat treatment of milk protein products improves the availability slightly, by about 1%. Processing of dried green peas destined for use in convenience food increases the protein availability by 20%.
    Notes: Zusammenfassung Zur Bestimmung der Bioverfügbarkeit von Aminosäuren aus Proteinen und proteinhaltigen Produkten wird die Fläche unter der postprandialen Plasmakonzentrations-Zeit-Kurve der Aminosäuren nach oraler Zufuhr berechnet. Dies geschieht nach Subtraktion der durch zirkadiane Rhythmen bedingten Leerwerte von den gemessenen Plasmakonzentrationen. Zur Ermittlung der relativen Bioverfügbarkeit von zwei Testpartnern, z.B. einem proteinhaltigen Produkt vor und nach einer bestimmten Behandlung oder zwei technologisch verschiedenen Zubereitungen eines bestimmten Proteins, genügt der Vergleich der beiden bereinigten Resorptionskurven. Hierzu werden die entsprechenden Mittelwertkurven des Probandenkollektivs verwendet, da die individuellen Verlaufskurven insbesondere durch diskontinuierliche Magenentleerung erhebliche Verzerrungen aufweisen. Durch die enzymatische Hydrolyse verschlechtert sich die quantitative Bioverfügbarkeit der Aminosäuren bei einem Lactalbumin um zwölf Prozent. Bei Produkten für die Kranken- bzw. Säuglingsernährung ist die Verfügbarkeit aus fertigen Flüssigprodukten um sieben bis zehn Prozent verbessert gegenüber den gleichartigen Trockenprodukten in Pulverform. Bei ultrahocherhitzten Milcheiweißprodukten wird die Verfügbarkeit gegenüber einfach sterilisierten geringfügig um etwa ein Prozent verbessert. Durch die Präparation getrockneter grüner Erbsen für die Verwendung in Fertiggerichten wird die Verfügbarkeit des Proteins um zwanzig Prozent gesteigert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01610081
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  • 2
    Electronic Resource
    Electronic Resource
    Bioavailability of sorbed- and separate-phase chemicals (1993)
    Springer
    Biodegradation 4 (1993), S. 141-153 
    Details
    ISSN: 1572-9729
    Keywords: bioavailability ; biodegradation ; sorption ; oil ; soil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00695116
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  • 3
    Electronic Resource
    Electronic Resource
    Comparison of the effects of two different galenical preparations of glyceryl trinitrate on pulmonary artery pressure and on the finger pulse curve (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 451-456 
    Details
    ISSN: 1432-1041
    Keywords: Glyceryl trinitrate spray ; pharmacokinetics ; a/b-ratio ; pulmonary artery diastolic pressure ; finger pulse curve ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course and the magnitude of the effect of glyceryl trinitrate (GTN) on central venous (pulmonary artery diastolic pressure-PAPd) and peripheral arterial (a/b-ratio of the finger pulse wave) haemodynamics were compared in a randomized double-blind cross-over study in 12 patients suffering from congestive heart failure (NYHA II–III) with elevated PADd at rest (≥15 mm Hg). The data were obtained in a bioavailability study of two sprays of glyceryl trinitrate, which differed in their galenical characteristics and in the dose of GTN (0.4 mg vs. 0.8 mg). Following sublingual administration of each spray, PAPd, a/b-ratio and the plasma concentrations of GTN and its metabolites were measured up to 30 min. The relative bioavailability of GTN of the test preparation was estimated to be 157%, 161% and 147%, when calculated from the plasma concentration-time data or the integrated effect of GTN on a/b-ratio or PAPd, respectively. The mean time courses of the decrease in PAPd and the increase in the a/b-ratio of the finger pulse curve were mirror images. Thus, there was a strong correlation between the mean values of PAPd and a/b-ratio following the administration of glyceryl trinitrate. Since the slope of the relationship differed considerably between the patients, the magnitude of effect of GTN on PAPd in the individual patient could not be predicted from the changes in a/b-ratio.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315542
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  • 4
    Electronic Resource
    Electronic Resource
    Absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin from different regions of the gastrointestinal tract in man (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 473-476 
    Details
    ISSN: 1432-1041
    Keywords: dDAVP ; bioavailability ; gastrointestinal tract ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP) from different regions of the gastrointestinal (GI) tract (stomach, duodenum, jejunum, ileum, colon, rectum) has been studied in 6 healthy, male volunteers aged 24 to 35 years, followed for 12 h after each drug administration. For i. v. administration the subjects received 4 μg dDAVP. For intestinal administration 400 μg dDAVP was directly applied to six distinct sites in the GI tract via two or four channel tubes with or without a distal occlusive balloon. Biological effects were assessed and plasma and urinary levels of dDAVP were measured using a specific, sensitive RIA. Urine osmolality remained elevated and diuresis decreased for 12 h following dDAVP administration irrespective of the site of application. After i. v. administration, the half-life of elimination of dDAVP was 60.0 min, plasma clearance 1.7 ml·min−1·kg−1, amount excreted in urine 2.0 μg and renal clearance was 0.8 ml·min−1·kg−1. The mean bioavailability (f) after gastric application was 0.19% (range 0.02–0.35%). f was 0.24% after duodenal application (range 0.04–0.62%), 0.19% after jejunal (range 0.01–0.41%), 0.03% after distal ileal (range 0.01–0.08%), 0.04% after proximal colonic (range 0.01–0.12%) and 0.04% after rectal (0.01–0.10%) application. The bioavailability was significantly higher in the three upper GI regions in comparison to the three lower regions. The bioavailability of dDAVP after gastric, duodenal and jejunal application was similar to that after swallowing a tablet in a previous study. Absorption from the ileum was lower than expected and no preferential site of absorption was found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315546
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  • 5
    Electronic Resource
    Electronic Resource
    Dose proportional absorption of 25–150 mg atenolol (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 305-306 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; bioavailability ; intestinal absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271380
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  • 6
    Electronic Resource
    Electronic Resource
    Bioavailability of controlled release carbamazepine estimated by mixed effect modelling (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 231-235 
    Details
    ISSN: 1432-1041
    Keywords: Carbamazepine ; kinetics ; population pharmacokinetics ; bioavailability ; controlled release ; non-linear model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption properties of a conventional tablet of carbamazepine (T) and a controlled release form of carbamazepine (TCR) have been compared using a nonlinear mixed effect model (NONMEM). Plasma carbamazepine concentration data were obtained from an open, steady-state, crossover bioavailability study in which 494 measurements were obtained from 13 patients, with an equal number of samples per patient for each dosage form. The pharmacokinetic model used was a one-compartment open model with first-order absorption and elimination. The objective function was used as a measure of the goodness of fit of the model to the data. Body weight was an important determinant of carbamazepine clearance (CL) but not volume of distribution (V). Accounting for the interindividual variability in volume of distribution did not significantly influence the objective function. Including different rates of absorption (ka) for the two dosage forms resulted in a significant improvement in the objective function, as well as reducing the interindividual variability in the rate of absorption. Adding a parameter for relative bioavailability (f) of TCR improved the objective function statistically, but an unrealistic value for V was obtained, and the absorption and elimination rates appeared to be transposed in the classical “flip-flop” manner. Fixing V to the value obtained before introducing f did not change the objective function and permitted estimation of f without the confounding influence of excessive parameters. The final population parameter estimates (standard error of estimate) were: CL, 0.0522 (0.0019) l·h−1·kg−1; V, 63.7 (FIXED)l; kaT, 0.312 (0.064) h−1; kaTCR, 0.149 (0.016) h−1; f, 1.01 (0.0326); variance (additive) in CL, 0.291 (0.083) (l·h−1·kg−1)2; residual intrasubject error variance (additive), 0.572 (0.082) (mg·l−1)2. The 95% confidence interval of the extent of absorption (f) of 93.6%–107.4% was well within the generally accepted range of ±20%, while the rate of absorption of Tegretol CR was significantly slower than that of Tegretol, as expected for a controlled release product.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271363
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  • 7
    Electronic Resource
    Electronic Resource
    Comparative study of availability of prednisolone after intestinal infusion of prednisolone metasulfobenzoate and prednisone (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 395-399 
    Details
    ISSN: 1432-1041
    Keywords: Prednisone ; Prednisolone metasulfobenzoate ; bioavailability ; intestinal infusion ; absorption ; presystemic clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of intestinal absorption in the differential availability of prednisone (PN) and prednisolone metasulfobenzoate (PO-MS), which might account for clinical resistance to PO-MS, has been studied by an infusion technique. In a randomized cross-over design trial, a solution in isotonic saline of PN or PO-MS (115 mg·l−1 was infused at 5 ml·min−1 for 2 h, into a 25 cm segment of jejunum in 8 healthy fasting subjects. The intestinal content was partly collected and the flow rate at the end of the test segment was determined by using a water movement marker (PEG 4000). Plasma, intestinal and urine concentrations of PN and PO were determined by liquid chromatography. From the data on PO, the active molecule, the systemic availability of PO-MS was significantly smaller than of PN, with the respective mean AUCs being 1.71 and 3.60 mg·h−1. The difference was associated with smaller mean Cmax, 0.20 vs 0.64 mg·l−1, higher mean tmax, 2.94 vs 2.06 h and lower mean ka, 0.98 vs 2.18 l/h after PO-MS. No significant difference was found in the half-life or renal clearance of the formulations tested. The mean MRT was significantly increased after PO-MS, 6.82 vs 5.30 h. The observed difference probably reflected a difference in intestinal absorption. The mean absorption in the test segment of PO-MS was significantly smaller at 17.4 vs 85.5% for PN. The ester form may be a limiting factor in the intestinal absorption of PO. Therefore, the choice of PN or PO-MS should follow the therapeutic indication, depending on whether a major systemic effect or a prolonged intestinal local effect is preferred.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316481
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  • 8
    Electronic Resource
    Electronic Resource
    Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 73-78 
    Details
    ISSN: 1432-1041
    Keywords: Thiamin ; thiamin monophosphate ; thiamin diphosphate ; distribution ; thiamin elimination ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then decreased to its initial value within 12 h in all but one subject; the half-life was 96 min. Thiamin mono and -diphosphate increased moderately (56%), and decreased slowly; the half-life of diphosphate was 664 min. Within 24 h, 53% of the administered dose was recovered in the urine, indicating a restricted distribution. After oral administration, the peak thiamin concentration in plasma was reached after 53 min and the concentration then had increased to 179% of its initial value. The elimination half-life was 154 min, and only 2.5% of the given dose was recovered in the urine. The relative bioavailability of thiamin was 5.3%. A moderate amount of the administered thiamin was stored in blood. Other body tissues must play an important part, therefore, in the distribution of thiamin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315284
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of iron deficiency anaemia and its treatment on single dose phenytoin bioavailability (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 387-388 
    Details
    ISSN: 1432-1041
    Keywords: Iron deficiency anaemia ; Phenytoin ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Iron deficiency is a common nutritional deficiency, which leads to structural functional and enzymatic changes in the body that may affect the pharmacokinetics of drugs. The present study in 7 normal volunteers and 8 adult male patients with irondeficiency anaemia (IDA) was done to investigate the effect of iron deficiency and its treatment with total dose iron (TDI) on the bioavailability of a single dose of phenytoin. Phenytoin bioavailability was investigated before and 3 and 28 days after TDI. The bioavailability parameters Cmax, tmax, AUC and 2 h phenytoin concentrations were not significantly different in anaemic patients as compared to normal volunteers before or after treatment, except for an increase in tmax 28 days after TDI treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265961
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of pantoprazole following single intravenous and oral administration to healthy male subjects (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 575-578 
    Details
    ISSN: 1432-1041
    Keywords: Pantoprazole ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma pharmacokinetics of pantoprazole have been investigated following single intravenous infusion and single oral administration at a dose of 40 mg to 12 healthy male subjects in a randomised cross-over study. Both treatments were generally well tolerated and no relevant compound-related adverse events were noted. The plasma pharmacokinetics of pantoprazole following intravenous infusion in this group of subjects were characterised by a total plasma clearance of 0.13 l·h−1·kg−1 and apparent terminal elimination half-life 1.9 h. The apparent volume of distribution estimated at steady state (0.171·kg−1) was compatible with the localization of a major fraction of the compound in extracellular water. Following oral administration as an enteric-coated tablet formulation, a variable onset of absorption was followed by rapid attainment of maximum plasma concentrations of pantoprazole. Pantoprazole was well absorbed following oral administration; the absolute systemic bioavailability of the compound was estimated as 77% (95% CI, 67 to 89%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02440862
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  • 11
    Electronic Resource
    Electronic Resource
    On the bioavailability of 2-chloro-2′-deoxyadenosine (CdA) (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 579-582 
    Details
    ISSN: 1432-1041
    Keywords: 2-Chloro-2′-deoxyadenosine (CdA) ; omeprazole ; food ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral CdA (0.24 mg/kg) was studied in 4 patients (1 with hairy cell leukaemia and 3 with B-cell chronic lymphocytic leukaemia) to determine any effect of food and fasting with and without omeprazole. Food intake did not significantly influence the bioavailability of CdA (42% after food intake vs 46% while fasting) but it did reduce the maximum plasma concentration (Cmax) by 40%; 83 compared to 116 nM while fasting. The time to reach maximum concentration (tmax) was delayed about 0.8 h after food intake. Pretreatment with omeprazole did not significantly influence the bioavailability of CdA (51% vs 46% without), or the interindividual variability in bioavailability in the fasting state (C.V. 0.26 with and C.V. 0.27 without). In conclusion, there was a small, though not statistically significant reduction in the bioavailability of CdA after food intake. Omeprazole did not significantly improve the bioavailability of CdA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02440863
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of oral tiopronin (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 79-84 
    Details
    ISSN: 1432-1041
    Keywords: Tiopronin ; 2-Mercaptopropionylglycine ; bioavailability ; urinary excretion ; cystine urolithiasis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten healthy subjects were given 500 mg (3064 μmol) tiopronin, or 2-mercaptopropionylglycine (2-MPG) by mouth. Cmax was reached after 3–6 h, and after a shorter β-phase a long terminal half-life of 53 h of total tiopronin was found. Tiopronin measured as unbound (non-protein-bound) drug disappeared more rapidly from plasma, with a calculated t 1/2 of 1.8 h. Mean residence time was higher (58 h) when calculated as total tiopronin than as unbound tiopronin (6 h), and this was also the case for the volume of distribution (Vλ=4551 vs Vλ,u=41 1). The results indicate extensive protein binding in plasma and a deep pool of tissue bound tiopronin after the first absorption and distribution phases. Absolute bioavailability (f) was 63%, and bioavailability calculated from urinary excretion was 47%, which are well correlated with each other. Urinary excretion was mainly confined to the first 6 h (74%) and was almost complete (98%) within 12 h. We conclude that the maximal absorption of the tiopronin was late, protein and tissue binding of the drug were high and its bioavailability varied. The renal excretion of low molecular weight tiopronin occurred early, which implies that the drug should be given in divided doses, at least twice daily, for optimal efficiency in the treatment of cystinuria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315354
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  • 13
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and β-blocking effects of transdermal timolol (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 493-495 
    Details
    ISSN: 1432-1041
    Keywords: Timolol ; β-adrenoceptor antagonist ; transdermal ; percutaneous absorption ; skin ; pharmacokinetics ; bioavailability ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic profiles of transdermal timolol 6 and 24 mg (as 5 and 20% w/v patches) was studied in four healthy young volunteers. To assess its bioavailability, the pharmacokinetics of an IV infusion of timolol maleate 5 mg was also determined in the same subjects. When the 20% (w/v) timolol patch was applied, the mean bioavailability was 74.4%. Plasma timolol concentrations were below the detection limit when a 5% patch was applied to the same skin area in all four subjects, except for one in whom the bioavailability was 23.6%. Weak erythema developed at the application site in all of the volunteers after application of the 20% (w/v) patch. However, erythema did not develop in any volunteer when the 5% patch was applied. The β-blocking effect was determined by exercise testing. Similar plasma levels generated similar changes in exercise-induced heart rate after the transdermal and intravenous administration of timolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315551
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  • 14
    Electronic Resource
    Electronic Resource
    Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 169-172 
    Details
    ISSN: 1432-1041
    Keywords: Fenspiride ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml·min−1, and its apparent volume of distribution was moderately large (2151). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng·ml−1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315501
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  • 15
    Electronic Resource
    Electronic Resource
    Use ofEnteromorpha intestinalis (Chlorophyceae) for active biomonitoring of heavy metals in the weser estuary (1993)
    Springer
    Aquatic ecology 27 (1993), S. 189-195 
    Details
    ISSN: 1573-5125
    Keywords: heavy metals ; biomonitoring ; bioavailability ; Enteromorpha intestinalis ; Weser estuary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The present study was planned to assess the validity ofEnteromorpha intestinalis for an active biomonitoring of heavy metals in the Weser estuary. Exposure of cultured algae (active biomonitoring) was carried out in 1987 and 1988, simultaneouslyEnteromorpha spp. was collected from the banks (passive monitoring) in the estuary. Cd, Pb, Ni, Zn and Cu contents of exposed algae were higher than the metal content of collected algae. Metal contents of both collected and field algae varied significantly over space and time. Bioconcentration factors and results of linear regression analysis indicate, that the bioavailability of Cu and Ni varies with regard to the sampling location but cannot be calculated from heavy metal concentration in the water. Due to the different metal and species specific bioavailability, we want to stress the need to monitor contamination of organisms directly. An active biomonitoring usingE. intestinalis will establish a rationale to compare contamination of different estuaries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02334782
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  • 16
    Electronic Resource
    Electronic Resource
    Application of a simplified method to determine bioavailability of an oral dose of phenytoin (1993)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 21 (1993), S. 195-208 
    Details
    ISSN: 1573-8744
    Keywords: bioavailability ; phenytoin ; Michaelis-Menten kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of capsules of phenytoin was determined by two methods: a method involving the numerical integration of the Michaelis-Menten equation and an alternative method involving fitting the time course of plasma concentrations, following the administration of the reference intravenous dosage, to an empirical quadratic function of time. The latter procedure requires much simpler computations. The two methods yielded very similar estimates of the rate and extent of absorption of phenytoin. Total absorption was 0.90±0.05 and 0.89±0.05(x±SE, n=6)using the methods of numerical integration and quadratic curve fitting, respectively. Both methods indicated that the rate of absorption of phenytoin was inconsistent and slow. Half the total absorption of phenytoin occurred over 2.5 ±0.3 hr but the remainder was absorbed very slowly over a period of about 30 hr. Empirical functions may be more generally useful in the determinations of the bioavalability of drugs, particularly if some aspects of the disposition are saturable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059770
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  • 17
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    Electronic Resource
    Correlation Between the Disintegration Time and the Bioavailability of Vitamin C Tablets (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 239-242 
    Details
    ISSN: 1573-904X
    Keywords: vitamin C ; ascorbic acid ; disintegration ; dissolution ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The goal of this study was to examine if the current USP disintegration standard for vitamin C tablets (max. 30 min in water at 37°C with disks) is adequate or if a tighter disintegration standard (e.g., European compendia max. 15 min) should be recommended based on bioavailability considerations. Four formulations of 500-mg vitamin C tablets ranging in mean disintegration time from 9 to 120 min were compared with a standard vitamin C solution in a double-blind clinical trial with 15 subjects. The products were administered with a standard breakfast. The data show that a solution of vitamin C and a fast-disintegrating tablet (8–9 min) have equal but significantly lower bioavailability than tablets with longer disintegration times (30, 60, 120 min). Tablets with a mean disintegration time of 60 min showed the highest bioavailability. When the disintegration test was performed without disks, disintegration times increased so much that only the tablets with the fastest disintegration time (which were also the tablets with the lowest bioavailability) met the current USP disintegration time limit. Based on the results of the study, changes in the USP standard to omit the disks or to shorten the disintegration time will not achieve enhanced bioavailability but will result in reduced vitamin C absorption. In vitro dissolution of vitamin C tablets did not show the traditional relationship with bioavailability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018938911420
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  • 18
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    Evidence for an Interaction Between the β-Blocker Pafenolol and Bile Salts in the Intestinal Lumen of the Rat Leading to Dose-Dependent Oral Absorption and Double Peaks in the Plasma Concentration–Time Profile (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 879-883 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; oral absorption ; double peaks ; absorption interaction ; intestinal excretion ; bioavailability ; dose dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Pafenolol is a β-blocker with unusual oral absorption properties. The blood concentration–time profile exhibits two peaks, and the bioavailability is low and dose dependent because of incomplete and nonlinear intestinal uptake. We addressed the question whether the intestinal absorption of pafenolol was affected by bile depletion in the gut lumen of rats. Further, the hypothesis that variable gastric emptying accounts for double peaks in blood was tested by duodenal administration of pafenolol. Following intraduodenal administration to rats with intact bile secretion, double peaks were observed in the blood concentration–time curve. The bioavailability was 6.8 ± 0.7% for the low dose (1 µmol/kg) and increased significantly to 28 ± 10% following the high duodenal dose (25 µmol/kg). These blood concentration–time profiles exclude interrupted gastric emptying as cause of the twin peaks. In bile duct-cannulated rats the intestinal absorption of the low dose (1 µmol/kg) was still poor (F = 10.7 ± 5.5%) and the blood concentration–time profile contained two peaks. Following administration of a high duodenal dose (25 µmol/kg) to rats with an almost bile-free small intestine, the absorption rate increased and the double-peak phenomenon disappeared in five of seven rats, while the bioavailability increased significantly, to 62 ± 27%. These results suggest that the low bioavailability of pafenolol is due to a complexation between bile and pafenolol in the gut lumen, preventing intestinal uptake in the major part of the small intestine. Further, such complex formation in the intestinal lumen may be the underlying mechanism of the double peaks observed in the blood concentration–time profile.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018965328626
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  • 19
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    In Vivo/in Vitro Correlation of Experimental Sustained-Release Theophylline Formulations (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 588-592 
    Details
    ISSN: 1573-904X
    Keywords: theophylline ; sustained release ; bioavailability ; deconvolution ; in vivo/in vitro correlation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A novel multiparticulate sustained-release theophylline formulation, which consisted of spherical drug pellets coated with a rate-controlling membrane, was evaluated in vivo. Two preparations that differ solely in the coat thickness, and hence rate of in vitro drug release, were studied in comparison with a solution of the drug. Both preparations produced serum concentration profiles that are reflective of a slow and sustained rate of absorption. The in vivo release versus time profiles calculated using a deconvolution procedure showed that the two preparations differed in the rate but not the extent of drug release. Satisfactory correlation was also obtained between the in vivo and the in vitro results. When the two preparations were further compared using the parameters, time to reach peak concentration (T p), peak concentration (C p), and total area under the serum concentration versus time curves (AUC), a statistically significant difference was observed in the T p and C p values but not the AUC values, suggesting that the preparations differed in the rate but not the extent of absorption. In addition, the extent of absorption from both preparations was comparable to that obtained with the drug solution.
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    URL: http://dx.doi.org/10.1023/A:1018910421840
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  • 20
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    Clinical Pharmacokinetics and Relative Bioavailability of Oral Procaterol (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 603-605 
    Details
    ISSN: 1573-904X
    Keywords: procaterol ; bronchodilator ; healthy volunteers ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and relative oral bioavailability of procaterol, an orally active β2-adrenergic agonist bronchodilator were evaluated in healthy volunteers. Procaterol was rapidly absorbed after oral administration. Mean plasma procaterol concentration–time profiles and pharmacokinetic parameters for both formulations were essentially superimposable. Following tablet administration, the mean C max was 358 pg/mL and the corresponding mean t max was 1.6 hr. Mean renal clearance was 163 mL/min and accounted for approximately one-sixth of the mean apparent oral plasma clearance (988 mL/min). The mean apparent elimination half-life of procaterol was 4.2 hr. Hepatic metabolism appears to be the primary mechanism for elimination of procaterol from the body, and first-pass metabolism may limit systemic bioavailability.
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    URL: http://dx.doi.org/10.1023/A:1018966506819
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  • 21
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    In Vivo Validation of the Release Rate and Palatability of Remoxipride-Modified Release Suspension (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1020-1026 
    Details
    ISSN: 1573-904X
    Keywords: remoxipride ; modified release ; suspension ; bioavailability ; convolution ; deconvolution ; dissolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Remoxipride, a D2-dopamine receptor antagonist, is well tolerated and completely absorbed after oral administration. Because of its extremely bitter taste, an oral palatable suspension was developed by using a taste-masking microencapsulation. The bioavailability of remoxipride was investigated in two studies in healthy volunteers after administration of a 100-mg dose in suspension. The first study used a capsule as reference, and the second study a plain solution. Taste assessment was carried out in the second study. The extent of bioavailability was the same when comparing the oral suspension to a capsule and to a plain solution. However, the rate of absorption is delayed, and Tmax was 3.0 hr after the suspension, 1.0 hr after the oral solution, and 1.6 hr after the capsule. The release rate in vitro from the suspension was determined by applying the USP-paddle method. By using numerical convolution and deconvolution, the release rates in vivo and in vitro were shown to be similar when using water with 0.5% sodium lauryl sulfate as dissolution liquid. The taste-masked oral suspension is suitable for full-scale production, with good control of the encapsulation process and of the preparation of a suspension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018966823600
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  • 22
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    Effect of Sodium Acid Pyrophosphate on Ranitidine Bioavailability and Gastrointestinal Transit Time (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1027-1030 
    Details
    ISSN: 1573-904X
    Keywords: ranitidine ; effervescent tablet ; absorption ; bioavailability ; bioequivalence ; sodium acid pyrophosphate ; gastrointestinal transit time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract During development of a ranitidine effervescent oral solution dosage form, a marked decrease was observed in the extent of ranitidine absorption relative to the conventional oral tablet. Two studies were conducted in healthy volunteers to confirm the involvement of an excipient, SAPP (sodium acid pyrophosphate), and the mechanism of interaction, altered gastrointestinal transit. The first study (n = 12) involved single-dose crossover comparisons of (A) 150 mg ranitidine with 1132 mg SAPP versus (B) 150 mg ranitidine and (C) 150 mg ranitidine with all the effervescent tablet excipients except SAPP versus (D) a 150-mg ranitidine effervescent tablet, all administered as oral solutions. Serum ranitidine AUC, C max, and t max were compared using two one-sided t test 90% confidence intervals (CI). Comparing treatments A to B and D to C, all 90% CI were below the 80–120% range, indicating significantly less extensive ranitidine absorption (54% based on AUC) from the oral solutions containing SAPP. The second study (n = 12) was a single-dose crossover comparing 50 µCi 111InCl solutions with and without 1132 mg SAPP. Gastrointestinal transit times, determined by scintigraphic imaging, were compared between treatments. Gastric emptying time was unchanged, but small intestinal transit time was decreased to 56% in the presence of SAPP. More rapid small intestinal transit associated with an excipient of a solution dosage form apparently resulted in a decreased extent of ranitidine absorption. This observation contradicts the conventional wisdom that oral solutions are unlikely to fall short of bioequivalence relative to solid oral formulations.
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    URL: http://dx.doi.org/10.1023/A:1018918907670
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  • 23
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    Biopharmaceutics of Didanosine in Humans and in a Model for Acid-Labile Drugs, the Pentagastrin-Pretreated Dog (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1157-1164 
    Details
    ISSN: 1573-904X
    Keywords: didanosine ; pentagastrin-pretreated dog ; formulation development ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Didanosine is a purine nucleoside analogue approved for the treatment of human immunodeficiency virus infection. It is extremely unstable at pH values less than 3 and requires protection against gastric acid-induced hydrolysis. Beagle dogs pretreated with pentagastrin, an analogue of gastrin that reproducibly stimulates gastric acid secretion, have been used to screen different didanosine formulations. The absolute bioavailability of didanosine from a saline solution decreased from approximately 43% in untreated dogs to 8% after pretreatment with pentagastrin. Administration of buffered solution of didanosine to untreated and pretreated dogs yielded bio-availability estimates of 37 and 30%, respectively. In humans, the bioavailability from a similar buffered solution was approximately 40%. Pentagastrin-pretreated dogs were used to evaluate four new products relative to a citrate-phosphate buffer sachet, the formulation selected for large-scale clinical trials in humans. Two of these new formulations, a chewable tablet and an antacid suspension, were more bioavailable then the reference sachet. This also proved to be true in man, necessitating an adjustment in the dose of didanosine when administered as the chewable tablet. Dogs pretreated with pentagastrin accurately predicted the improved bioavailability of new didanosine formulations prior to clinical use. This animal model may be helpful in evaluating the biopharmaceutics of other acid-labile drugs.
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    URL: http://dx.doi.org/10.1023/A:1018964117665
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  • 24
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    A Floating Controlled-Release Drug Delivery System: In Vitro-in Vivo Evaluation (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1321-1325 
    Details
    ISSN: 1573-904X
    Keywords: floating ; controlled release ; theophylline ; gastric retention time ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a density of 0.67 was prepared and compared in vitro and in vivo to Theo-dur. The in vitro release rate of the floating tablet was slower. In vivo scintigraphic studies for a floating and a heavy nonfloating tablet, under fasting and nonfasting conditions, showed that the presence of food significantly increased the gastric retention time for both tablets, and tablet density did not appear to make a difference in the gastric retention time. However, the positions of the floating and nonfloating tablets in the stomach were very different. Bioavailability studies in human volunteers under both fasting and nonfasting conditions showed results comparable to those with Theo-dur. The floating controlled-release theophylline tablet maintained constant theophylline levels of about 2 mg/mL for 24 hr, which may be attributable to the release from the agar gel matrix and the buoyancy of the tablet in the stomach.
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    URL: http://dx.doi.org/10.1023/A:1018921830385
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  • 25
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    The effect of phytase on the availability of P from myo-inositol hexaphosphate (phytate) for maize roots (1993)
    Springer
    Plant and soil 154 (1993), S. 189-196 
    Details
    ISSN: 1573-5036
    Keywords: bioavailability ; maize ; myo-inositol ; phosphorus ; phytase ; phytin ; soil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The effect of adding phytase to the root medium of maize plants on the P-availability of added myo-inositol hexaphosphate (phytin) has been studied in pot experiments. When 40 mM phytin-P in nutrient solution was incubated in quartz-sand for 15 days in the absence of plants, 80% of it could be recovered from the solution as soluble organic P. Maize plants growing on this mixture assimilated P from phytin at rates comparable to those from inorganic phosphate (Pi). At a lower addition rate (2 mM phytin-P) only 10% was recovered in the soil solution, and plant growth was severely limited by P. At this low phytin level, the addition of phytase (10 enzyme units per kg sand) increased the plants' dry weight yield by 32%. The relative increases of the Pi concentration in the solution and of the amount of P in the plants were even higher, indicating that the observed growth stimulation was due to an increased rate of phytin hydrolysis. The enzyme-induced growth stimulation was also observed with plants growing in pots filled with soil low in P, when phytin was added. However, on three different soils the addition rates of phytin and phytase necessary for obtaining a significant phytase effect were both about 10 times higher than those required in quartzsand. It is concluded that the P-availability from organic sources can be limited by the rate of their hydrolytic cleavage.
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    URL: http://dx.doi.org/10.1007/BF00012524
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  • 26
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    Bio-availability of phosphorus in sediments of the western Dutch Wadden Sea (1993)
    Springer
    Hydrobiologia 253 (1993), S. 151-163 
    Details
    ISSN: 1573-5117
    Keywords: Wadden Sea ; sediments ; phosphorus compounds ; bioavailability ; algae ; iron ; calcium redox potential ; oxygen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The purpose of this study was to make a prognosis of the effects of extended purification of terrestrial waste water, reaching the Wadden Sea by the River Rhine and Lake IJssel, on the phosphate concentration in the western Wadden Sea. The quantities of different phosphorus fractions in intertidal and subtidal sediments of the Marsdiep tidal basin (western Dutch Wadden Sea) were measured. Different methods are applied to determine the amount of phosphorus that can be released from these sediments. The direct bioavailability is determined by inoculating sediment suspensions with a natural mixture of precultured micro-organisms from the sampling area. A second approach is the measurement of the phosphate release under different redox conditions. Sequential extraction of sediment samples with different solvents is also applied. Under the present conditions and compared to the nutrient loads from fresh water (Lake IJssel) and from the North Sea, the phosphorus stored in the sediments of the western Dutch Wadden Sea plays a minor role in the total supply to micro-algae and bacteria. The bulk of the biologically available phosphorus in the sediments originates from the metal-associated fraction. Releasable phosphate may contribute to the local annual primary production to an extent of ca 45 to ca 150 g C m−2 a−1. The total amount of phosphorus in the sediment (mainly calcite associated) is twice to 6 times the biologically available amount.
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    URL: http://dx.doi.org/10.1007/BF00050735
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  • 27
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    Seasonal variation of acid volatile sulfide concentration in sediment cores from three northeastern Minnesota lakes (1993)
    Springer
    Hydrobiologia 271 (1993), S. 87-95 
    Details
    ISSN: 1573-5117
    Keywords: acid volatile sulfide ; metal ; bioavailability ; sediment ; freshwater ; temperature ; seasonal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Acid volatile sulfide (AVS) is a natural agent in sediments which complexes some cationic metals and thereby influences the toxicity of these metals to benthic organisms. Because of its influence on metal bioavailability, AVS has been proposed as a key normalization phase for the development of sediment quality criteria for metals. However, studies conducted primarily in marine and estuarine systems have shown that AVS concentrations can vary markedly both temporally and with (sediment) depth. In this study, AVS concentrations were measured monthly for 16 mo in several segments of sediment cores from three freshwater lakes: Caribou Lake, Fish Lake and Pike Lake in northeastern Minnesota, USA. The concentrations of AVS in cores from the three lakes varied inversely with sediment depth. AVS concentrations also varied seasonally by as much as two orders of magnitude and were directly correlated with changes in water temperature. The correlation between AVS and temperature likely was related both to changes in primary productivity and sediment microbial activity.
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    URL: http://dx.doi.org/10.1007/BF00007545
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    Molecular diagnostics of polycyclic aromatic hydrocarbon biodegradation in manufactured gas plant soils (1993)
    Springer
    Biodegradation 4 (1993), S. 303-321 
    Details
    ISSN: 1572-9729
    Keywords: bioavailability ; bioluminescence ; gene probe ; in situ microbial analysis ; mRNA ; polynuclear aromatic hydrocarbons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Traditional methods for quantifying specific catabolic bacterial populations underestimate the true population count due to the limitations of the necessary laboratory cultivation methods. Likewise,in situ activity is also difficult to assess in the laboratory without altering the sample environment. To circumvent these problems and achieve a truein situ bacterial population count and activity measurement, new methods based on molecular biological analysis of bacterial nucleic acids were applied to soils heavily contaminated with polycyclic aromatic hydrocarbons (PAH). In addition, a naphthalene-lux reporter system was used to determine bioavailability of naphthalene within these soils. DNA extracted from seven PAH-contaminated soils and hybridized with thenahA gene probe indicated that the naphthalene degradative genes were present in all samples in the range of 0.06 to 0.95 ng/100 µl DNA extract which was calculated to represent 3.2×106 to 1.1×1010 cells/g soil (assuming one copy of these genes per cell).14C-naphthalene mineralization was observed in all contaminated soils with14CO2 mineralization rates ranging from 3.2×10−5 to 304,920.0×10−5 µg g soil−1h−1. Phenanthrene, anthracene, and benzo(a)pyrene were mineralized also in several soils. Messenger RNA transcripts ofnahA were isolated and quantified from 4 soils. Only one soil tested, soil B, was inducible with salicylate above thein situ nahA gene transcript level. Two of the soils, C and G, were already fully inducedin situ. The naphthalene mineralization rate correlated positively with the amount ofnahA gene transcripts present (r=0.99). Naphthalene was bioavailable in soils A, D, E, G, and N as determined by a bioluminescent response from the naphthalene-lux reporter system. Taken together, these data provided information on what the naphthalene-degrading bacterial population was experiencingin situ and what approaches would be necessary to increase activity.
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    URL: http://dx.doi.org/10.1007/BF00695976
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  • 29
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    Regional Gastrointestinal Absorption of the Beta-Blocker Pafenolol in the Rat and Intestinal Transit Rate Determined by Movement of 14C-Polyethylene Glycol (PEG) 4000 (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 130-135 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; oral absorption ; intestinal permeability ; bioavailability ; double-peaks ; dose dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The gastrointestinal absorption characteristics of pafenolol following oral administration as a solution in man and rat has previously been found to be a double-peak phenomenon and exhibited dose-dependent bioavailability, despite negligible presystemic metabolism. In both man and rat the first peak appeared approximately 0.5–1 hr postdose and the second, more pronounced peak 3–4 hr postdose. In rat more than 90% of the available dose was absorbed during the second peak. In the present study we investigated the absorption of a solution of pafenolol in rats after intrajejunal and intraileal administration. The resulting blood concentration–time profile of pafenolol exhibited one peak only; the extent of absorption was similar to that observed when the same dose was given orally. The small intestinal transit time of the 14C-PEG 4000 solution was found to be more than 3 hr. The transit rate was higher in the proximal part of the small intestine compared to the more distal part, where the transit of the solution was staggered. In conclusion, the results of the intestinal transit time investigation and the administrations of pafenolol at different levels of the alimentary tract indicate that pafenolol is a drug with a specific absorption site located in the ileocolonic region.
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    URL: http://dx.doi.org/10.1023/A:1018993501426
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  • 30
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    The Effect of Gastric pH on the Absorption of Controlled-Release Theophylline Dosage Forms in Humans (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1037-1045 
    Details
    ISSN: 1573-904X
    Keywords: controlled-release theophylline ; pH-dependent dissolution ; achlorhydric humans ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The bioavailability of three marketed controlled-release dosage forms and a reference solution of theophylline was studied in eight subjects with normal gastric fluid acidity and seven subjects who were achlorhydric. Gastric pH was monitored with a Heidelberg capsule. One of the controlled-release dosage forms dissolved more rapidly in vitro when exposed to acid conditions, one dissolved more rapidly in pH 7.5 media, and the third dissolved at a rate independent of pH. Using a crossover design, each subject received each dosage form twice. Blood was sampled for up to 47 hr after each dose, and serum was assayed for theophylline by HPLC. The product which dissolved more rapidly under acid conditions in vitro exhibited a 3 hr longer T max in the achlorhydrics compared to the normal subjects. The product which dissolved more rapidly in the pH 7.5 media exhibited a relatively higher AUC(0–∞) in the achlorhydric subjects than in normal subjects after the AUC data were normalized for clearance differences between the two subject groups. The in vivo bioavailability of these dosage forms could be related to the in vitro dissolution characteristics for some parameters. However, with the exception of the mean T max values, the mean bioavailability parameters differed by less than 20% between the two subject groups.
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    Intranasal Absorption of a Kappa Agonist Analgesic (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1083-1086 
    Details
    ISSN: 1573-904X
    Keywords: kappa agonist analgesic ; nasal absorption ; bioavailability ; pharmacokinetics ; ED50.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018987328143
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  • 32
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    Gelatin-Acacia Microcapsules for Trapping Micro Oil Droplets Containing Lipophilic Drugs and Ready Disintegration in the Gastrointestinal Tract (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1115-1122 
    Details
    ISSN: 1573-904X
    Keywords: nonhardened gelatin–acacia microcapsules ; complex coacervation ; bioavailability ; lipophilic drugs ; O/W emulsions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Nonhardened gelatin-acacia microcapsules were studied for encapsulation of microdroplets of oil solution containing a lipophilic drug as core material and ready disintegration with release of micro oil droplets in the gastrointestinal tract. Probucol and S-312-d, a Ca-channel blocker, were employed as model lipophilic drugs. Glyceryl tricaprylate and tricaprate mixture solutions containing these drugs were encapsulated according to the complex coacervation method and were recovered as free-flowing powders without any hardening (cross-linking) step. The microcapsules obtained were disintegrated, and the emulsion was reproduced within 3 min at 37°C in the first or second test solution defined in the Japanese Pharmacopeia XII. When the microcapsules were stored as a powder at room temperature in a closed bottle, no significant change in their appearance or disintegration time upon rehydration was observed even after 1 year. Oral bioavailabilities of model drugs from the microcapsules were tested in rats and dogs and compared with those from other conventional formulations. Gastrointestinal absorption of both probucol and S-312-d from the microcapsules was remarkably more efficient than that from other formulations such as powders, granules, or oil solution. The proposed method for microencapsulation could be useful for powdering drug-containing oil solutions or O/W emulsions while maintaining excellent bioavailability.
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    URL: http://dx.doi.org/10.1023/A:1018951814939
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    Synthesis and Evaluation of Morpholinoalkyl Ester Prodrugs of Indomethacin and Naproxen (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1191-1199 
    Details
    ISSN: 1573-904X
    Keywords: indomethacin ; naproxen ; prodrugs ; hydrolysis kinetics ; solubility ; partition coefficient ; ulcerogenicity ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Morpholinoalkyl esters (HC1 salts) of naproxen 1 and indomethacin 3 were synthesized and evaluated in vitro and in vivo for their potential use as prodrugs for oral delivery. Prodrugs were freely soluble in simulated gastric fluid (SGF) and pH 7.4 phosphate buffer and showed a minimum of a 2000-fold increase in solubility over the parent drugs. All prodrugs were more lipophilic than parent drugs as indicated by n-octanol/pH 7.4 buffer partition coefficients but less lipophilic in terms of n-octanol/SGF partition coefficients. Potentiometrically determined pK a's for prodrugs were in the range of 6.89 to 8.62 at 25°C. All prodrugs were quantitatively hydrolyzed to their respective parent drugs by enzymatic and/or by chemical means. An increase in carbon chain length rendered the prodrugs more stable at pH 7.4 but less stable in SGF. The esters were generally found to be hydrolyzed rapidly in rat plasma at 37°C, the half-lives being in the range of 1.2–31.0 min. Based on in vitro results, prodrugs 2c and 4c were chosen to evaluate solid-state stability, in vivo bioavailability, and ulcerogenicity. At elevated temperatures, the solid-state decomposition of 2c and 4c followed biphasic kinetics, with rapid decomposition occurring initially. The prodrugs were 30–36% more bioavailable orally than the parent drugs following a single equimolar solution dose in rats. Prodrugs 2c and 4c were significantly less irritating to gastric mucosa than parent drugs following single-dose and chronic oral administration in rats.
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    URL: http://dx.doi.org/10.1023/A:1018976520391
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    The Dissolution and Bioavailability of Etodolac from Capsules Exposed to Conditions of High Relative Humidity and Temperatures (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1295-1300 
    Details
    ISSN: 1573-904X
    Keywords: dissolution ; bioavailability ; etodolac capsules ; stressed conditions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The dissolution and bioavailability of etodolac from capsules exposed to high relative humidity and temperature were compared to those from capsules stored at room temperature (RT). Dissolution of stressed and control capsules was evaluated using a USP basket apparatus at 100 rpm with 900 mL pH 7.5 phosphate buffer (0.05 M) at 37°C. The dissolution of etodolac from capsules exposed to stressed conditions was also evaluated with enzymes (pancreatin, 1%, w/v) added to the dissolution medium. The bioavailability of etodolac from capsules exposed to stressed conditions was compared in both dogs and humans to capsules stored at RT conditions. Capsules, 200 and 300 mg, exposed to stressed conditions failed the dissolution (without enzymes) specification [not less than 85% released (80% Q) in 30 min]. However, upon enzyme addition, all capsules met the specification. The rate and extent of absorption from these 200 and 300 mg etodolac capsules in dogs were equivalent to those from capsules stored at RT conditions that passed the dissolution specification. Similarly, the bioavailability of etodolac from 300 mg capsules that failed the dissolution specification upon exposure to stressed conditions was equivalent to that of control capsules in 24 adult male volunteers. Thus, an in vitro dissolution test with enzymes provides a better indication of stressed capsule performance in vivo.
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    URL: http://dx.doi.org/10.1023/A:1018913628568
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    Absorption of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) from Rat Nasal Mucosa (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1372-1377 
    Details
    ISSN: 1573-904X
    Keywords: granulocyte colony-stimulating factor (rhG-CSF) ; recombinant human granulocyte-CSF ; nasal absorption in rats ; bioavailability ; leukocyte number
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. The relative bioavailability of rhG-CSF for subcutaneous administration was ∼2%, as evaluated from the immunologically active rhG-CSF concentration in rat plasma and the area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. Pharmacological availability relative to subcutaneous administration was determined from the increase in total blood leukocyte numbers. The pharmacological availability was 5–10%, determined from the AUC for the increased ratio of total leukocyte numbers versus time for 48 hr; it was slightly dependent on the pH and the osmotic pressure of the dosing solution. Accordingly, the plasma concentration of rhG-CSF did not always reflect its pharmacological effects. Relative bioavailability and pharmacological availability were increased about 23 times and 3 times, respectively, by polyoxyethylene 9-lauryl ether (Laureth-9), but no increase in availability occurred with sodium glycocholate. The increase in total leukocyte numbers was maintained during multiple rhG-CSF dosing, and the addition of Laureth-9 further increased the pharmacological effects of this agent. This study indicates that nasal administration of rhG-CSF is an effective parenteral administration route.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018990318090
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