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  • pharmacokinetics  (84)
  • bioavailability  (27)
  • Springer  (97)
  • 1980-1984  (97)
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  • Springer  (97)
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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of zimelidine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    Details
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562618
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  • 2
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of chlordiazepoxide in patients with alcoholic hepatitis (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 279-285 
    Details
    ISSN: 1432-1041
    Keywords: chlordiazepoxide ; alcoholic liver disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r=0.73, P〈0.0005) and was independent of the presence of alcoholic hepatitis. The metabolic clearance of chlordiazepoxide was significantly lower in the patients than in the normal subjects (7.6 compared to 13.8 ml/kg-h, P〈0.005). Linear regression analysis revealed a significant correlation between clearance and albumin (r=0.77, P〈0.00005). However, the predictive value of this relationship was shown to be minimal. Multiple regression analysis produced only a slight improvement in the correlation when both albumin and lactate dehydrogenase were used as variables (r=0.83, P〈0.00005). In six of the patients, a second clearance study was conducted three weeks following their initial one. All repeat subjects showed improvement both clinically and as reflected by their laboratory tests for liver injury, but there was not a significant change in their clearance of chlordiazepoxide. Multiple regression analysis of the clearance data on the initial and repeat subjects showed a significant correlation between clearance and the variables age, albumin, and lactate dehydrogenase (r=0.91, P〈0.0025). This relationship suggests that over a short period of time (where age can be considered constant) changes in albumin and lactate dehydrogenase could be potentially useful in predicting clearance changes in a single individual.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562805
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  • 3
    Electronic Resource
    Electronic Resource
    The influence of duration of intravenous infusion of an acute dose on plasma concentrations of cimetidine (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 29-34 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; intravenous infusion ; pharmacokinetics ; peptic ulcer ; duration of infusion ; acute dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of cimetidine administered by bolus intravenous injection to critically ill patients has been associated with serious cardiac arrhythmias, due presumably to high initial plasma concentrations. The aim of this study was to determine the range of infusion times of a single 200 mg dose of cimetidine which would avoid high initial drug concentrations while maintaining a duration of effective concentrations no less than that resulting from bolus injection. Computer simulations of both maximum plasma cimetidine concentrations and duration of effective plasma cimetidine concentrations versus duration of infusion were based on mean pharmacokinetic date from 6 peptic ulcer patients who had received cimetidine 200 mg i.v. over 5 min. The simulations indicated that to reduce maximum plasma cimetidine concentrations by at least 50%, while maintaining the duration of effective plasma concentrations, the infusion time should be at least 30 min and no longer than 4.5 h. The validity of the simulations was subsequently tested in 4 of the patients, who received cimetidine 200 mg i.v. over 30 min. The mean maximum plasma concentration for the 30 min infusion (4.57±0.53 µg/ml) was, as predicted, approximately half that corresponding to bolus administration in these patients (8.97±1.96 µg/ml). Moreover, the duration of effective concentrations for the infusion (1.43±0.28 h) was significantly greater than that for the 5 min infusion (1.21±0.31 h). We suggest that where an acute intravenous dose of cimetidine (200 mg) is indicated, it should be administered over at least 30 min rather than as a bolus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544010
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  • 4
    Electronic Resource
    Electronic Resource
    Evaluation of medigoxin in outpatients (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 251-258 
    Details
    ISSN: 1432-1041
    Keywords: medigoxin ; digoxin ; dissolution rate ; proportionality ; bioavailability ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We compared our ability to predict the dose of medigoxin and of digoxin required to achieve a fixed serum concentration (the dose requirement) in 33 outpatients. Preliminary work supported the assumptions that the steady state glycoside concentration achieved was proportional to the daily dose given to an individual, and that the bioavailability of the different tablet presentations was similar for either glycoside. We were not able to predict the dose requirement from patient characteristics with any more certainty for medigoxin than for digoxin. Not only the between-patient variability in dose requirement, but also the within-patient variability, was similar for the two glycosides. However the digoxin used had a dissolution rate of over 90% in 1 h. When comparing medigoxin with digoxin of lower, or more variable dissolution rate, medigoxin may be preferable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562801
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  • 5
    Electronic Resource
    Electronic Resource
    Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 647-649 
    Details
    ISSN: 1432-1041
    Keywords: tobramycin ; newborn infants ; intrapatient variations ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p〉0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p〉0.05), and elimination half-life averaged 8.6 and 7.1 h (p〉0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants ⩽1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p〈0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p〈0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants ⩽1.5 kg birth weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543504
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  • 6
    Electronic Resource
    Electronic Resource
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    ISSN: 1432-1041
    Keywords: acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395207
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of propranolol during pregnancy (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 583-587 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32 and 36 weeks gestation and when at least 6 weeks postparum. On both occasions, subjects were given propranolol 120 mg orally or 10 mg intravenously in randomised order with a minimum washout period of 1 week. Propranolol was assayed in plasma by gas-liquid chromatography with electron-capture detection and the pharmacokinetic parameters were investigated. There were no significant alterations in elimination half-life, clearance or apparent volume of distribution per kilogram antenatally compared with postnatally: bioavailability was also unchanged. It is concluded that the disposition of propranolol is not altered during pregnancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556896
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of diltiazem after intravenous and oral administration (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 349-352 
    Details
    ISSN: 1432-1041
    Keywords: diltiazem ; pharmacokinetics ; intravenous dose ; oral dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetic profile of diltiazem, a novel calcium antagonist, was studied in 12 volunteers following oral (60 mg) and intravenous (15 mg) administration. After i.v. administration biphasic elimination was observed, with a distribution half-life of 0.3±0.2 h and an elimination half-life of 3.1±1.0 h; the apparent volume of distribution was 5.3±1.71/kg and the total clearance was 1.28±0.48 l/kg/h. After the oral dose the elimination phase had a half-life of 3.2±1.3 h. The absolute bioavailability of diltiazem ranged from 24 to 74% (mean 42±18%). The interindividual variation may be explained by a variable first pass effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610053
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  • 9
    Electronic Resource
    Electronic Resource
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    ISSN: 1432-1041
    Keywords: acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553155
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  • 10
    Electronic Resource
    Electronic Resource
    Bioavailability and diurnal variation in absorption of sustained release theophylline in asthmatic children (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 667-672 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; asthma ; children ; sustained-release ; diurnal ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absolute oral bioavailability of a sustained release theophylline tablet (Nuelin-SR250), given 12 hourly was determined in 14 asthmatic children aged 5 to 13 years. In 4 of the patients, mean bioavailability of the fourth dose was 38.9±8.4% and that of the sixth dose was 67.9±25.9% (p〈0.05) in the other ten patients. This suggests steady-state had not been achieved after four doses. In the initial study with 9 patients, a significant diurnal variation in predose plasma theophylline concentrations was observed, as the mean morning predose concentrations were 2.9 fold greater than the mean evening predose concentrations (p〈0.005). Dual peak plasma concentrations occurred in 5 out of the 9 patients. The mechanism of this diurnal variation was investigated in a further 5 asthmatic children (10.8 years ±1.6). Morning and night steady-state plasma theophylline concentrations during a continuous intravenous infusion of aminophylline were not different (14.9±5.3 mg/l vs. 15.6±5.9 mg/l), demonstrating that there was no diurnal variation in the plasma clearance of theophylline. The diurnal variation in predose concentrations with Neulin-SR250 was confirmed with the morning concentrations again being 2.6 fold greater than those in the evening. However, bioavailability was not significantly different for day (09.00–21.00) and night (21.00–09.00) dosing intervals after doses 6 and 7 respectively of Nuelin-SR250. The plasma concentration versus time profiles suggested that the diurnal variation in predose concentrations was due to slower absorption of the evening dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542356
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