European journal of clinical pharmacology
-
Eur. J. Clin. Pharmacol. · Jan 1996
Replacement of (R)-methadone by a double dose of (R,S)-methadone in addicts: interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics.
Twenty-two patients receiving (R)-methadone maintenance treatment were switched to a double dose of (R,S)-methadone: blood samples were collected before and after the change, and the concentrations of the enantiomers were measured. In the second period, during racemic methadone treatment, important interindividual variability in the stereoselective disposition of the enantiomers of methadone was measured, with (R)/(S) ratios ranging from 0.63 to 2.40. This point should be taken into account particularly with respect to therapeutic drug monitoring of racemic methadone. ⋯ Although of small amplitude (16%), this decrease confirms previously described adaptive changes in methadone pharmacokinetics during racemic methadone maintenance treatment and may necessitate, in some patients, a dose adjustment.
-
Eur. J. Clin. Pharmacol. · Jan 1996
Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate.
Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a systemic analgesic during labour. Recent reports of perinatal adverse effects prompted us to carry out therapeutic nalbuphine monitoring in obstetric analgesia. Because data on fetomaternal transfer are scarce and the pharmacokinetics of this drug in the neonate are largely unknown, we report data obtained from 28 parturients treated with nalbuphine either intramuscularly and/or intravenously during labour. ⋯ An estimated plasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuphine concentrations. Apart from a flattening of the fetal heart rate tracing in 54% of the cases, only one neonate had a low Apgar score at birth. The apparent prolonged half-life of nalbuphine in the neonate indicates the usefulness of an intramuscular injection of naloxone to prevent recurrence of cardiorespiratory depression due to nalbuphine administration to the mother.
-
Eur. J. Clin. Pharmacol. · Jan 1996
Population pharmacokinetics and pharmacodynamics of oral levodopa in parkinsonian patients.
The population pharmacokinetics and pharmacodynamics of a standardised oral test dose of levodopa have been determined in patients with mild to severe Parkinson's disease using parametric, non-linear mixed effect modelling with the program NON-MEM. Levodopa plasma concentration data and motor effect behaviour (tapping times) were obtained from 46 patients, for whom a total of 970 observations were available (approximately 21 pharmacokinetic and pharmacodynamic observations per patient). The pharmacokinetic-pharmacodynamic model used was a one-compartment first-order absorption model linked to the sigmoid EMax representation of the Hill equation via an equilibration rate-constant, ke0. The model was also tested via a reduction in the number of pharmacokinetic and pharmacodynamic data points to a total of four to eight per patient. ⋯ In a clinical setting knowledge of the population pharmacokinetic and pharmacodynamic parameters for oral levodopa may prove useful in estimating the duration of the drug's beneficial motor activity in patients with mild to severe Parkinson's disease (Hoehn and Yahr status I-IV).
-
Eur. J. Clin. Pharmacol. · Jan 1995
Randomized Controlled Trial Clinical TrialRecovery characteristics following anaesthesia with sevoflurane or propofol in adults undergoing out-patient surgery.
The aim of the study was to compare recovery characteristics in adult patients following general anaesthesia either with the new investigational volatile agent sevoflurane or with propofol. Accordingly, two groups of 25 adults undergoing outpatient surgery were entered into a prospective, randomised study. ⋯ Modified Aldrete scores were also higher in this group within the first hour after anaesthesia than in the propofol group. Sevoflurane appears to be a useful alternative to propofol in outpatient anaesthesia.
-
Eur. J. Clin. Pharmacol. · Jan 1995
Randomized Controlled Trial Comparative Study Clinical TrialComparative efficacy of hamamelis distillate and hydrocortisone cream in atopic eczema.
In a double-blind, randomized, paired trial lasting 14 days in 72 patients with moderately severe atopic eczema, hamamelis distillate cream (5.35 g hamamelis distillate with 0.64 mg ketone/100 g) was compared with the corresponding drug-free vehicle and 0.5% hydrocortisone cream, and reductions of the basic criteria of severe atopic eczema (delta values of the sum scores), i.e. itching, erythema and scaling, were evaluated. Thirty-six patients in each group were treated, which allowed the detection of a 10% difference between verum and control (confirmatory study). Effects were compared using Wilcoxon's test. ⋯ Unwanted cutaneous reactions occurred in six patients, although due to their inflammatory nature and their confinement to vehicle-treated patients, they may not represent true adverse effects but rather a lack of efficacy. The results prove the superiority of low-dose hydrocortisone cream over hamamelis distillate cream, and the therapeutic outcome following this preparation was no better than following the base preparation. The mild, yet unmistakable anti-inflammatory effect of hamamelis cream in experimental models of inflammatory skin disease was thus not reflected by an efficacy in patients with atopic eczema greater than that obtained from the base preparation.