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  • 1990-1994  (55)
  • 1935-1939
  • 1905-1909
  • 1993  (55)
  • pharmacokinetics  (55)
  • 1
    Electronic Resource
    Electronic Resource
    The pharmacokinetic and pharmacodynamic interactions of ramipril with propranolol (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 255-260 
    Details
    ISSN: 1432-1041
    Keywords: Ramipril ; Propranolol ; interaction ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for four days in a crossover, double-blind fashion. The pharmacokinetics of ramipril and ramiprilat were investigated on day 4. Effects on plasma renin activity, ACE activity, and heart rate and blood pressure both before and after a standardized exercise test were measured on days 1 and 4. On day 4 the combination reduced the mean arterial pressure by 2.8 mmHg compared with propranolol alone and by 3.7 mmHg compared with ramipril alone. Ramipril had no effect on the bradycardia induced by propranolol. Propranolol reduced exercise mean arterial pressure by 9 mmHg (day 4) and heart rate by 7 beats.min−1 (day 4) compared with ramipril; this was not affected by co-administration of ramipril. On day 4 the average plasma renin activity was not significantly higher than after the combination. ACE activity was not affected by propranolol. The pharmacokinetics of ramipril and ramiprilat were not influenced by propranolol. The combination of ramipril and propranolol has additive pharmacodynamic effects that may be useful in the treatment of hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315392
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of diclofenac on isradipine pharmacokinetics and platelet aggregation in volunteers (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 391-393 
    Details
    ISSN: 1432-1041
    Keywords: Isradipine ; Diclofenac ; pharmacokinetics ; platelet aggregation ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this open, two-period crossover study in 18 healthy male volunteers, a single oral dose of 50 mg diclofenac was administered alone and on day 7 of multiple oral dosing of 5 mg b.i.d. isradipine to assess a possible pharmacokinetic interaction. The effect of these drugs on ex vivo platelet function was also determined. Serial blood samples were obtained over 12-hour periods on three occasions: after the single diclofenac dose; after the morning dose of isradipine on day 6 and after co-administration of both drugs on day 7 of steady-state isradipine administration. Additional samples were taken at 2 h post dose for determination of ex vivo platelet aggregation. Isradipine plasma concentrations were determined by a gas chromatographic method and diclofenac plasma concentrations by an HPLC method. The pharmacokinetic characteristics of diclofenac were unaltered during co-administration. The maximum plasma concentration of isradipine was increased 19.6% during co-administration from 5.06 to 6.05 ng·ml−1. This is not expected to be of clinical importance. Isradipine's apparent total body clearance and steady-state AUC remained unchanged. Ex vivo induced platelet aggregation was not affected by any of the treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316480
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  • 3
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of the β2-adrenoceptor agonist, tulobuterol, given transdermally and by inhalation (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 361-364 
    Details
    ISSN: 1432-1041
    Keywords: Tulobuterol ; β2-adrenoceptor agonist ; aerosol inhalation ; transdermal delivery ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of tulobuterol given transdermally or by aerosol inhalation in healthy male volunteers. Tulobuterol was rapidly absorbed after inhalation, with a tmax of 0.8–1.5 h. The Cmax and the AUC increased linearly with dose. Tulobuterol was well absorbed after transdermal administration, with an absorption lag-time of about 4 h. The Cmax and AUC increased linearly with dose and the tmax was about 9–12 h. The mean percentage of drug absorbed during the application of a patch for 24 h was 82–90% after a single dose and 82–85% during repeated dosing. The mean urinary recoveries as unchanged drug after a single inhalation and patch application were 3–4% and 5–6% respectively. Tulobuterol did not accumulate during repeated inhalation or transdermal application. It was well tolerated, except for an increase in heart rate of 10–20 beats · min−1 after five repeated applications of a 4 mg patch.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316473
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  • 4
    Electronic Resource
    Electronic Resource
    Modelling circadian variation in the pharmacokinetics of non-steroidal anti-inflammatory drugs (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 357-361 
    Details
    ISSN: 1432-1041
    Keywords: Circadian rhythms ; Indomethacin ; Ketoprofen ; pharmacokinetics ; time-varying models ; nonsteroidal anti-inflammatory drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A one-compartment model with first-order absorption has provided good fits to five sets of indomethacin data and four sets of ketoprofen data taken at different times of day. There was substantial variation in the model parameters with time of administration and most of the features of this variation applied equally to both drugs. From the data examined, the source of variation appears to be mainly in the absorption phase and this was confirmed using a chronokinetic analysis, in which simultaneous fits were obtained with time-variant rate parameters. However, there may also be circadian variation in protein binding. The danger of quoting parameter values for either of these two drugs based on administration at a single time of day has been illustrated, and this may well be true for other drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265955
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  • 5
    Electronic Resource
    Electronic Resource
    The relation between type of renal disease and renal drug clearance in children (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 195-197 
    Details
    ISSN: 1432-1041
    Keywords: Cefotaxime ; Renal insufficiency ; desacetylcefotaxime ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is generally assumed that the renal clearance of drugs in patients with renal impairment are affected to a similar extent regardless of the type of renal disease (intact nephron hypothesis). We have studied the effect of underlying renal disease on the pharmacokinetics of cefotaxime and desacetylcefotaxime in two groups of children (ages 7 to 16 y) with varying degrees of renal dysfunction. Patients in group 1 (n=5) had intrinsic renal disease and those in group 2 (n=5) had extrinsic renal disease, as identified by the primary renal lesion. After a single intravenous dose of cefotaxime timed blood and urine samples were collected for 24 h; cefotaxime and desacetylcefotaxime were measured by HPLC. There were no significant differences between the groups in age, body surface area, urine output, creatinine clearance, total body clearance, nonrenal clearance, renal clearance, and volume of distribution at steady state of cefotaxime, and renal clearance of desacetylcefotaxime. However, the renal clearance: creatinine clearance (CLR:CLCR) ratios for both cefotaxime [1.34 in group 1 vs. 0.51 in group 2] and desacetylcefotaxime [1.58 in group 1 vs. 0.75 in group 2] were statistically significant between the two groups. Group 1 patients had an average CLR:CLCR ratio greater than 1 for both the parent compound and the metabolite, suggesting that net tubular secretion was still intact, despite a diminished glomerular filtration rate (CLCR=24 ml·min−1·1.73 m−2). In contrast, patients in group 2 (CLCR=49) ml·min−1·1.73 m−2) had an average CLR:CLCR ratio less than 1 for both cefotaxime and desacetylcefotaxime, suggesting that renal tubular transport mechanisms did not remain functional in these patients. Our findings suggest that the effect of renal insufficiency on the renal elimination of cefotaxime and its metabolite desacetylcefotaxime may depend on the cause of renal insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315480
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  • 6
    Electronic Resource
    Electronic Resource
    Lack of effect of magnesium-aluminium hydroxide on the absorption of theophylline given as a pH-dependent sustained release preparation (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 85-88 
    Details
    ISSN: 1432-1041
    Keywords: Theophylline ; Antacids ; Asthma ; slow-release formulations ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Antacids can modify the pharmacokinetic parameters of sustained-release preparations of theophylline by changing the gastric pH. Though this has been studied with various theophylline/antacid combinations, the specific preparations investigated here have not previously been tested. The objective of the study was to assess any change in the availability of theophylline from a sustained-release preparation (SR), induced by the coadministration with an antacid. The study was designed as a double-blind randomized crossover trial in the Pneumology Departments of three general hospitals. Fifteen patients were studied. They all had stable asthma treated with theophylline and no major organ failure or gastro-intestinal lesions requiring the use of antacids. The antacide (aluminium hydroxide 800 mg and magnesium hydroxide 800 mg), or placebo, tid, was added to a stable regimen of theophylline SR bid, for 4 days, in crossover fashion. Plasma theophylline concentrations were measured before and 1,2,3,4,6,8,10,12,16 and 24 h after the morning dose of Armophylline on the fourth day of each treatment period; the maximum plasma concentration (Cmax), and time to Cmax (tmax) were noted, and the area under the 24-h time-concentration curve (AUC0–24) and mean plasma concentration (Cmean) were computed. Peak expiratory flows on the same day, before and 3, 6 and 12 h after the morning dose of Armophylline were also measured. There was no change in any of the parameters studied. The addition of the antacide to theophylline, each given according to standard clinical practice, did not modify the pharmacokinetics of the latter. This result probably can not be generalized to all pairs of sustained-release theophylline-antacid preparations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315286
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  • 7
    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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  • 8
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and haemodynamic effects of continuous nicorandil infusion in healthy volunteers (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 437-443 
    Details
    ISSN: 1432-1041
    Keywords: Nicorandil ; vasodilator ; continuous infusion ; blood pressure ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics and haemodynamic effects of nicorandil after a 12-h infusion. Nicorandil is a mixed vasodilator combining the actions of a nitrate and a potassium channel opener. Nicorandil was infused for 12 h in 21 healthy volunteers at rates of 0.05, 0.10, and 0.20 μg·kg−1·min−1 using a placebo controlled, crossover design. Systemic blood pressure, heart rate, electrocardiographic (ECG) intervals, and cardiac output (impedance cardiography) were measured supine and standing. Dose-related, steady-state plasma nicorandil concentrations occurred within 3 to 4 h. Nicorandil's pharmacokinetics were linear with dose. Four 0.20 μg·kg−1·min−1 nicorandil infusions were terminated early primarily because of moderate or severe headaches. There were no safety concerns (ECG intervals, laboratory assays). Blood pressure fell versus placebo only in the standing position and heart rate increased slightly (not significant). That is, standing blood pressure in the 6 to 12 h interval fell from baseline 8.0*/6.8, 1.6/5.1, and 9.8*/7.9* mmHg (systolic/diastolic, *=P〈0.05 versus placebo) at 0.05, 0.10, and 0.20 μg·kg−1·min−1 respectively. Cardiac output increased slightly above placebo at lower doses. Haemodynamic changes correlated poorly with plasma nicorandil concentrations. Similar total doses were less well-tolerated when extended over 12 h. We saw no evidence of pharmacodynamic tolerance to nicorandil within 12 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315515
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of nocloprost in human volunteers and its relation to dose (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 497-500 
    Details
    ISSN: 1432-1041
    Keywords: Nocloprost ; PGE2-analoga ; clearance ; half life ; absolute bioavailability ; pharmacokinetics ; i. v. dose ; oral dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and absolute bioavailability of nocloprost, a synthetic PGE2-analogue with cytoprotective properties, was investigated in human volunteers as a function of the dose. Ten young male volunteers received nocloprost 5 μg i. v. and 100, 200 and 400 μg p.o. in random order at weekly intervals. Serum nocloprost levels were monitored for up to 12 h after each dose, using a specific, validated assay. After nocloprost 5 μg i. v. the highest serum level of 373 pg·ml−1 was found in the first sample 5 min after injection, and the subsequent decline showed one or two phases, with half-lives of 4 and 49 min. The AUC was 89 pg·h·ml−1, the total plasma clearance was 13.2 ml·min−1·kg−1, and the volume of distribution at steady state was 0.16 l·kg−1. After oral administration the maximum serum level and AUC increased in proportion to the dose. tmax showed a wide scatter, with an average value of about 30 min independent of the dose. Although not detectable in every subject, post maximum serum levels declined biphasically, with half-lives of ca 10 and 35–40 min. The absolute bioavailability after oral administration averaged about 2% and was independent of the dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315552
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  • 10
    Electronic Resource
    Electronic Resource
    Minor and clinically non-significant interaction between toloxatone and amitriptyline (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 97-99 
    Details
    ISSN: 1432-1041
    Keywords: Amitriptyline ; Toloxatone ; Depression ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of a pharmacokinetic interaction between amitriptyline and toloxatone (a new MAOI-A) has been studied in 17 depressed in-patients. Amitriptyline and its demethylated and hydroxylated metabolites in blood and urine were measured at steady state after the administration of amitriptyline with and without toloxatone in steady state. The metabolic status of patients was determined using the dextromethorphan phenotyping test. There was only a minor pharmacokinetic interaction between amitriptyline (AMT) and toloxatone, with a small increase in the AMT/NT (nortriptyline) plasma ratio: 0.68 before and 0.78 after toloxatone. The urinary excretion and plasma levels of AMT and its metabolites were not affected by the co-therapy. Three of the patients were poor metabolisers, but this did not predict the magnitude of the drug interaction. The interaction does not justify plasma level monitoring of amitriptyline as the change in pharmacokinetics was so small.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315289
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