We have studied the pharmacokinetics of oxybutynin (Ditropan) after single oral (5 mg) and intravenous administration (1 and 5 mg), and after repeated oral administration in healthy volunteers. Oxybutynin was rapidly absorbed, maximum plasma concentrations (8 ng.ml-1) being reached in less than 1 h. The absolute systemic availability averaged 6% and the tablet and solution forms displayed similar relative systemic availability. Plasma concentrations of oxybutynin fell biexponentially, the elimination half-life being about 2 h. There was a large interindividual variation in oxybutynin plasma concentrations. Almost no intact drug could be recovered in the urine. During repeated oral administration steady-state was reached after eight days of treatment. The low absolute systemic availability of oxybutynin, the large interindividual variability in its plasma concentrations, and the apparent absence of intact oxybutynin in the urine suggest that its major pathway of elimination is hepatic metabolism.
The debrisoquine/sparteine phenotype was determined in 51 patients with depression, who were subdivided into 3 groups in terms of their drug treatment. Log (MR) for each group was compared. Patients treated with benzodiazepines had the same distribution of log (MR) as the healthy population, but the distribution was shifted towards higher values in patients treated with neuroleptics and antidepressants. It appears that the phenotypic expression of debrisoquine oxidation may be modified by drugs whose metabolism follows the same route as debrisoquine. The debrisoquine test must be carefully interpreted in patients receiving several drugs in the same time.
1. Almitrine bismesylate displays wide inter‐subject variation in peak plasma concentrations and can induce peripheral polyneuropathy. 2. The phenotyped volunteer panel approach was used to examine whether almitrine oxidation displayed a genetic polymorphism of the debrisoquine/sparteine type. 3. There was no difference between poor and extensive metabolisers of debrisoquine with respect to the pharmacokinetics and metabolism of almitrine.
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