ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Permeability and clearance views of drug absorption: A commentary (1995)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 23 (1995), S. 333-337 
    Details
    ISSN: 1573-8744
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02354289
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    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
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of Levodopa and Carbidopa in Rats Following Different Routes of Administration (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 549-555 
    Details
    ISSN: 1573-904X
    Keywords: levodopa ; carbidopa ; rat ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This study examined the pharmacokinetics of levodopa and carbidopa in the rat after different modes of administration. The drugs were given simultaneously by the intravenous, intraarterial, oral, duodenal, and intraperitoneal routes, as single doses. The ratio of levodopa to carbidopa given was always 4:1. Two iv doses (5 and 15 mg/kg of levodopa) were given to test for nonlinearity. Three ip doses of levodopa were given (5, 7.5, and 15 mg/kg), and the 15 mg/kg dose was given in three volumes (2, 4, and 20 mL/kg). One oral dose and two intraduodenal doses of 15 mg/kg were given. The drugs were dissolved in saline in one of the intraduodenal doses and suspended in 1.8% methylcellulose in the other. The elimination of levodopa was nonlinear. There was a comparatively high degree of interindividual variability in absorption with the oral route, but this was substantially reduced when levodopa was given intraduodenally. There was also much less variability with the intraperitoneal route compared to the oral, and the degree of absorption was generally high. There was a significantly higher extent and slower rate of absorption when levodopa was administered ip in a large volume of vehicle. These results suggest that the oral route may not be the optimal method of delivering levodopa to patients who have a fluctuating response and that a continuous delivery system via the intraperitoneal or intraduodenal routes might be a better alternative.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018970617104
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Dose-Dependent Intestinal Absorption and Significant Intestinal Excretion (Exsorption) of the β-Blocker Pafenolol in the Rat (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 727-731 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; double peaks ; dose-dependent absorption ; intestinal excretion ; exsorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The elimination of [3H]pafenolol and metabolites was investigated in fasted and fed rats. Separate groups received intravenous doses (0.3 and 3.0 µmol/kg) and oral doses (1 and 25 µmol/kg). After iv administration of pafenolol, the excretion of unchanged drug into urine and feces was about 50 and 25–30% of the given dose, respectively. The predominating mechanism for the excretion of pafenolol into feces was intestinal excretion (exsorption) directly from blood into gut lumen, since only about 3% of a given iv dose was recovered as pafenolol in the bile. When the oral dose was raised from 1 to 25 µmol/kg, the mean (±SD) bioavailability, calculated from urine data, increased from 14 ± 9 to 30 ± 11% (P 〈 0.05) in the starved rats and from 14 ± 3 to 16 ± 3% in the fed animals. In parallel, the fraction absorbed from the gut (f a) increased from 19 ± 9 to 31 ± 10% in the starved rats and from 16 ± 4 to 19 ± 5% in the fed animals, respectively. This indicates that the low bioavailability is due primarily to poor intestinal uptake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018916017723
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Regional Rectal Perfusion: A New in Vivo Approach to Study Rectal Drug Absorption in Man (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 426-432 
    Details
    ISSN: 1573-904X
    Keywords: intestinal permeability ; rectal absorption ; perfusion ; bioavailability ; human drug absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Background: In vivo permeability measurements of drugs in the colonic/rectal region in humans are difficult. A new instrument for the perfusion of a defined and closed segment in the colon/rectum was developed. The objective of this study was to evaluate its use for studying drug absorption mechanisms in the human rectum and to investigate the effect of transmucosal water absorption on drug permeability. Six healthy subjects participated at 2 separate occasions by using a modified system for segmental rectal perfusion. The system consisted of a multichannel tube with inflatable balloons and was endoscopically introduced into the rectum. The technique was considered acceptable by the following criteria; (a) high and reproducible recovery of PEG 4000, (b) stable residence time of the solution within the test segment, (c) flux of electrolytes that agrees with previous reports, (d) mass-balance absorption of antipyrine across the rectal barrier, (e) and good acceptability to the subjects. The permeability of antipyrine in the rectal region was increased by inducing net water absorption. D-glucose was not absorbed during any study periods. The present technique is valuable for studying drug absorption from the human rectum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016216905197
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    The Influence of Net Water Absorption on the Permeability of Antipyrine and Levodopa in the Human Jejunum (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 1540-1544 
    Details
    ISSN: 1573-904X
    Keywords: permeability ; net water flux ; solvent drag ; active drug absorption ; levodopa ; antipyrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Food ingestion can influence the absorption of levodopa in the intestine and thereby contribute to fluctuations of motor functions in Parkinson patients. Obstruction of the active transport of levodopa by amino acids can be one factor. Paracellular drug absorption, a route proposed to be influenced by net transport of water across the intestinal epithelium, might occur for a small and hydrophilic drug such as levodopa. In the present study we studied how luminal L-leucine (60 mmol/L), alone or combined with hypotonicity, might stimulate net water absorption, and levodopa uptake in the human small intestine, since this possibly can contribute to the variable intestinal absorption of levodopa. The Loc-I-Gut perfusion technique was used in 10 healthy volunteers to study the effects of induced net fluid absorption on the small intestinal absorption of levodopa (2.5 mmol/L). An induced net fluid absorption was observed only when L-leucine was combined with a hypoosmolar perfusion solution. However, this did not enhance the intestinal permeability of levodopa. In conclusion, we suggest that the variability in the absorption of levodopa in Parkinson’s disease cannot be explained by differences in transmucosal water flux in the human small intestine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018941200575
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Comparison Between Permeability Coefficients in Rat and Human Jejunum (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1336-1342 
    Details
    ISSN: 1573-904X
    Keywords: bioavailability ; in situ-in vivo correlation ; intestinal perfusion ; intestinal permeability ; oral absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Our main aim is to determine the effective intestinal permeability (Peff) in the rat jejunum in situ for 10 compounds with different absorption mechanisms and a broad range of physico chemical properties, and then compare them with corresponding historical human in vivo Peff values. Methods. The rat Peff coefficients are determined using an in situ perfusion model in anaesthetized animals. The perfusion flow rate used is 0.2 ml/min, which is 10 times lower than that used in humans. The viability of the method is assessed by testing the physiological function of the rat intestine during perfusions. Results. The Peff for passively absorbed compounds is on average 3.6 times higher in humans compared to rats (Peff,man = 3.6 · Peff,rat + 0.03·10−4; R^2 = 1.00). Solutes with carrier-mediated absorption deviate from this relationship, which indicates that an absolute scaling of active processes from animal to man is difficult, and therefore needs further investigation. The fraction absorbed of drugs after oral administration in humans (fa) can be estimated from 1 − e−(2·P eff,man ·t res /r·2.8). Conclusions. Rat and human jejunum Peff estimates of passively absorbed solutes correlate highly, and both can be used with precision to predict in vivo oral absorption in man. The carrier-mediated transport requires scaling between the models, since the transport maximum and/or substrate specificity might differ. Finally, we emphasize the absolute necessity of including marker compounds for continuous monitoring of intestinal viability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016065715308
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    A New Approach for Direct In Vivo Dissolution Studies of Poorly Soluble Drugs (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 1490-1492 
    Details
    ISSN: 1573-904X
    Keywords: in vivo dissolution ; Loc-I-Gut ; Carbamazepine ; sparingly soluble drugs ; intestinal perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012149511768
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Rat Jejunal Permeability and Metabolism of μ-Selective Tetrapeptides in Gastrointestinal Fluids from Humans and Rats (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 1780-1785 
    Details
    ISSN: 1573-904X
    Keywords: enkephalin analogues ; oral drug delivery ; peptide absorption ; intestinal perfusion ; intestinal metabolism ; protease inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study intestinal transport and metabolism of three new μ-selective tetrapeptide enkephalin analogues, LEF537, LEF553 and TAPP These peptides are stabilized against enzymatic hydrolysis by having a D-aminoacid in position 2 and a blocked COOH-terminal. Methods. We used a single-pass perfusion technique to study the transport of the peptides in rat jejunum. To reduce luminal and/or brush-border metabolism during the perfusion we used protease inhibitors (Pefabloc® SC, bestatin and thiorphan). The rate of metabolism was studied by incubations in rat jejunal homogenate, rat jejunal fluid and human gastric and jejunal fluid with and without these inhibitors. Results. The jejunal permeabilities (Peff) of the peptides were 0.43−0.78 ⋅10−4 cm/s without inhibitors and 0.09−0.45 ⋅10−4 cm/s in presence of the inhibitors. All three peptides were rather rapidly degraded by enzymes in rat jejunal homogenate with half-lives of between 11.9 ± 0.5 and 31.7 ± 1.5 min. The addition of inhibitors to the homogenate prolonged the half-lives substantially for LEF553 (167 ± 35 min) and TAPP (147 ± 2 min), but only slightly for LEF537 (16.4 ± 0.5 min). LEF553 and TAPP were both hydrolyzed in rat and human jejunal fluid, while LEF537 was metabolized less in these fluids. When LEF553 and TAPP were incubated with intestinal fluid in the presence of inhibitors, metabolism was almost completely inhibited. There was no metabolism for any of the peptides in human gastric juice. Conclusions. The replacement of the terminal free carboxylic group with an amide group did not increase the stability of the peptides in jejunal tissue enough to allow successful oral drug delivery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012144232666
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    Characterization of Fluids from the Stomach and Proximal Jejunum in Men and Women (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 497-502 
    Details
    ISSN: 1573-904X
    Keywords: drug dissolution ; gastrointestinal fluids ; in vitro/in vivo correlation ; variability ; gender differences ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To chemically characterize the fluids available for drug dissolution in the upper gastrointestinal tract during the fasted state in humans, and to examine variations and potential gender differences regarding the physico-chemical properties of these fluids. Methods. Twenty-four healthy volunteers, 12 females and 12 males, were intubated, and fluids from the stomach and upper jejunum were collected separately. Bulk pH, osmolality, electrolytes and total concentrations of bile acids and proteins were assessed. To study intraindividual variations, eleven of the individuals were studied on more than one occasion. Results. The stomach and upper jejunal fluids varied significantly in all the measured entities, except the total concentration of proteins. The intraindividual variability was pronounced in some of the individuals, both in the stomach and the upper jejunum. We did not, however, observe any gender differences. Conclusions. This study demonstrates the complex nature of the fluids available for drug dissolution in the stomach and the upper small intestine in humans. The results can be used when designing a more physiological in vitro dissolution media representative for the fasted state. When designing such a medium, we suggest that gender differences not be taken into account.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012107801889
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...