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  • pharmacokinetics  (165)
  • Springer  (165)
  • American Association of Petroleum Geologists
  • Frontiers Media SA
  • Institute of Physics
  • Wiley
  • 2020-2024
  • 2010-2014
  • 1995-1999  (31)
  • 1985-1989  (134)
  • 1920-1924
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Publisher
  • Springer  (165)
  • American Association of Petroleum Geologists
  • Frontiers Media SA
  • Institute of Physics
  • Wiley
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Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 543-552 
    ISSN: 1432-1041
    Keywords: thiopentone ; anaesthesia ; intravenous anaesthesia ; multi-stage infusion ; exponential infusions ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Several multi-stage infusion regimens and a computer controlled exponentially decreasing infusion regimen were evaluated in twelve patients undergoing head and neck surgery or neurosurgery. Thiopentone dosage was based on the mean of pharmacokinetic parameter values from the literature and adjusted for each patient's lean body mass in order to rapidly achieve a predetermined plasma thiopentone concentration of 15 or 20 µg/ml in the period following the initial bolus dose to induce anaesthesia. Anaesthesia was satisfactory in all cases. Plasma thiopentone concentrations were maintained between 10–20 µg/ml during infusion in the five patients who received either a four or five stage infusion and in the six patients who received the exponential infusion, but not in the single patient who received a two-stage infusion. The mean recovery time was 111 min. The plasma concentrations of total and unbound thiopentone at awakening showed little intersubject variability, despite considerable differences in total dose and duration of infusion, suggesting the absence of acute tolerance to the drug. Plasma clearance of total thiopentone correlated strongly with calculated lean body mass and to a lesser extent with total body weight suggesting that lean body mass, in particular, should be an accurate predictor of thiopentone maintenance dose requirements. This study shows that it is feasible to use thiopentone as a primary anaesthetic agent during surgery by administering the drug either as an exponentially decreasing infusion or as an infusion comprising 4 or 5 stepwise decreasing rates.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 589-595 
    ISSN: 1432-1041
    Keywords: antipyrine ; chronic renal failure ; drug metabolism ; metabolism ; cumulation ; renal excretion ; pharmacokinetics ; clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.
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  • 3
    ISSN: 1432-1041
    Keywords: primaquine ; malaria ; acute and chronic dosing ; carboxylic acid metabolite ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of primaquine (PQ) and its major carboxylic acid metabolite (PQC) have been studied in seven Indian patients withP. vivax malaria following PQ 15 mg/day p.o. for 14 days. After a single oral dose on Day 1, a mean peak blood concentration of 50.7 ng/ml PQ was attained after 2.3 h, which declined monoexponentially with a half-life of 5.6 h. The mean total body clearance was 37.6 l/h and the volume of distribution was 2921. The mean renal excretion (0–24 h) of the drug was only 0.54% of the dose and renal clearance was 0.189 l/h. Following chronic administration, none of the pharmacokinetic parameters was affected, and a steady state blood concentration of 2.5–4.2 ng/ml PQ was attained. After the first dose of PQ, PQC had a mean area under the blood concentration — time curve 11-fold higher than that of the parent drug. In contrast to the rapid distribution and elimination of PQ, the metabolite showed a longer mean residence time and accumulation in the body. The mean Cmax and AUC of the metabolite on Day 14 were 48 and 40% higher than the corresponding Day 1 values. The metabolite could not be detected in urine at any time in any patient. PQ and its metabolite did not show any accumulation in blood cells.
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  • 4
    ISSN: 1432-1041
    Keywords: salbutamol ; sublingual ; oral ; inhaled ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 µg (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggests that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.
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  • 5
    ISSN: 1432-1041
    Keywords: salbutamol ; asthma ; controlled-release formulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion. At steady-state the geometric mean values for Cmax were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median tmax values were 300 and 240 min respectively. The geometric mean AUC (0–12) were 4507 ng·min·ml−1 and 8980 ng·min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572. There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 48 (1995), S. 273-277 
    ISSN: 1432-1041
    Keywords: Mesalamine ; 5-aminosalicylic acid ; controlled release capsules ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 μg · ml−1 and 1.33 μg · ml−1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 531-534 
    ISSN: 1432-1041
    Keywords: ketoconazole ; pharmacokinetics ; antimycotic drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of the anti-mycotic ketoconazole in seven patients who took it for 1–6 months at a dose of 200 mg daily. The mean elimination half-life of the drug was 3.3 h, and although the ketoconazole was given only once daily, a satisfactory clinical response was obtained in all seven individuals. Only a small fraction of the absorbed drug (mean 0.22%) was excreted unchanged in the urine, suggesting almost complete metabolism. Our results support the concept that anti-mycotic activity in the tissues continues after the plasma drug concentration has fallen below a critical level. Our results also support the concept of a change in pharmacokinetics with chronic dosing.
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  • 8
    ISSN: 1432-1041
    Keywords: triazolam ; troleandomycin ; benzodiazepines ; antibiotics ; drug interaction ; pharmacokinetics ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy volunteers received a single oral dose of triazolam 0.25 mg after 7 days on troleandomycin 2 g/day p.o. or placebo in a double-blind cross-over study. Plasma triazolam and psychometric and memory tests (including Critical Flicker Fusion threshold, Choice Reaction Time, Digit Symbol Substitution and Self-Rating Scales) were assessed at regular intervals after the final treatment. Troleandomycin was found to prolong the psychomotor impairment and amnesia produced by triazolam. There was a significant enhancement of the AUC, the peak concentration and the delay to tmax of triazolam after 7 days treatment with troleandomycin compared to placebo. Thus, there is a pharmacokinetic interaction, and the combination of triazolam and troleandomycin should be avoided or the dose of triazolam should be adjusted. The most likely mechanism is a diminished hepatic first-pass effect, and a decrease in the apparent oral clearance of triazolam.
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  • 9
    ISSN: 1432-1041
    Keywords: nisoldipine ; cirrhosis ; pharmacokinetics ; blood pressure ; heart rate ; calcium entry blocker ; concentration-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and effects on blood pressure and heart rate of nisoldipine were studied in 8 patients with cirrhosis and in 8 age-matched healthy controls. On separate occasions each subject received nisoldipine by i.v. infusion (0.37 mg in 40 min) and as a tablet (5 mg for patients and 20 mg for control subjects). After i.v. nisoldipine, the elimination half-life was 9.7 h in control subjects and 16.6 h in the cirrhotics. The volume of distribution was 4.1 l/kg and 6.4 l/kg and the total systemic clearance was 847 ml/min and 494 ml/min, respectively. On oral nisoldipine, systemic availability was fourfold higher in patients with cirrhosis: 14.7% versus 3.7%. After i.v. administration of nisoldipine there was a brief decrease in systolic and diastolic blood pressure in both groups, whereas the heart rate increased. After 4 h a second effect peak appeared in the control subjects. After oral nisoldipine similar effect-time profiles were found, but effects lasted longer than after i.v. administration. Comparison of the maximal total plasma concentration of nisoldipine and the maximal effect in the two groups revealed that sensitivity to nisoldipine was not different in patients with cirrhosis. A reduction in the dose of nisoldipine is recommended when cirrhotics require oral nisoldipine in therapeutic practice.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 659-664 
    ISSN: 1432-1041
    Keywords: BTS 49465 ; hypertension ; pharmacokinetics ; blood pressure effect ; heart rate effect ; side-effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and haemodynamic effects of a 200 mg oral dose of BTS 49465 (7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) were investigated in a double-blind placebo controlled study. BTS 49465 was rapidly absorbed and cleared from the systemic circulation with a half-life of 1.6 h by oxidation to the sulphone metabolite. The metabolite was cleared with a half-life of 37.6 h. Saliva concentrations of both BTS 49465 and its metabolite correlated well with the plasma concentrations. Compared to placebo, BTS 49465 produced statistically significant reductions in blood pressure and increases in heart rate both supine and after a 60° head up tilt. The time course of the haemodynamic changes suggested that the sulphone metabolite contributed to the overall hypotensive response. Plasma Renin Activity was only marginally elevated and there was no evidence of acute fluid retention. BTS 49465 was well tolerated in terms of haematological and biochemical parameters and subjective side-effects.
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