A randomized controlled trial comparing the ef®cacy of controlled-release oxybutynin tablets (10 mg once daily) with conventional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were stabilized on 5 mg twice daily of oxybutynin Objective To compare the ef®cacy of a controlled-release (CR) formulation of oxybutynin with that of conventional oxybutynin in patients with detrusor instability or detrusor hyper-re¯exia whose symptoms were stabilized on conventional oral oxybutynin tablets. Patients and methods The study comprised a randomized, double-blind, parallel-group trial involving 130 patients drawn from 15 centres in the UK. The study was of 6 weeks' duration, i.e. 2 weeks of screening whilst taking conventional oxybutynin tablets (5 mg twice daily) followed by 4 weeks of double-blind treatment with either CR oxybutynin tablets (10 mg once daily) or conventional oxybutynin tablets (5 mg twice daily). Outcome measures were changes in 24-h frequency and 24-h incontinence episodes recorded throughout the study on diary charts. Adverse events were recorded by patients in their diary charts and serum concentrations of oxybutynin and its active metabolite, N-desethyloxybutynin, were measured at baseline and at completion of the study to detect possible drug accumulation. Results The treatments did not differ signi®cantly in any of the outcome measures. The primary ef®cacy criterion was the daytime continence at completion of the study; 53% and 58% of patients were continent on CR and conventional oxybutynin treatments, respectively (the 95% con®dence interval of the difference in the proportion being x22% to 13%; P = 0.62). The total number of side-effects experienced by those patients receiving treatment with the CR formulation was 57% of that for patients receiving treatment with conventional oxybutynin. Individual side-effects showed a similar distribution within treatment groups. There was no evidence of the accumulation of oxybutynin or N-desethyloxybutynin during the multiple dosing of CR or conventional oxybutynin tablets. Conclusion The CR and conventional formulations of oxybutynin did not differ in their ef®cacy, and the CR formulation was associated with fewer side-effects. In addition, CR oxybutynin appeared to maintain therapeutic blood levels over the 24 h dosing interval with no accumulation of oxybutynin or its active metabolite. Once-daily dosing with a CR tablet is seen as convenient for the patient and is expected to result in improved compliance in patients already stabilized on conventional oxybutynin treatment.

Ahstyuct; Oxybutynin has an extensive first pass metabolism after oral administration. the main active metabolite being N-desethyloxybutynin. The purpose of this study was to investigate the CYP isoform specificity of oxybutynin N-deethylation and possible interactions. Oxybutynin N-deethylation in human liver microsomes in vifro was potently inhibited by ketoconazole (ICso 4.5 pM), less and variably by itraconazole and not by quinidine or several other reference inhibitors, suggesting that CYP3A enzymes are predominant catalysts of the reaction. Recombinant CYP3A5 enzyme had higher activity in oxybutynin N-deethylation than recombinant CYP3A4. Ketoconazole inhibited oxybutynin N-deethylation by the recombinant CYP3A4 and CYP3A5 almost completely, whereas itraconazole inhibited the activity of CYP3A4 more potently than that of CYP3A5. Oxybutynin inhibited CYP3A4-and CYP2D6-associated activities (testosterone 68-hydroxylase and dextromethorphan 0-demethylase. respectively) in human liver microsomes. CYPl A l/2-, CYPZAh-, CYP2C9-and CYPZEI-associated activities were inhibited less potently or not at all by oxybutynin when compared with reference inhibitors. Although the reasons for the weak and variable inhibition by itraconazole remain to be studied. it seems that oxybutynin is predominantly metabolized by CYP3A4 and CYP3A5 hut not by CYP2D6. However, it seems to have some affinity also to the latter enzyme.

Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.

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Abstracl:The effect of time interval between food and drug ingestion on the bioavailability of oxybutynin was investigated in a randomized, three-phase cross-over study in 3 1 healthy volunteers. The serum concentrations of oxybutynin and the metabolite, N-desethyloxybutynin were measured up to 48 hr after ingestion of a controlled-release 10 mg oxybutynin tablet either in fasting state, 2 hr after breakfast or I hr before. The C , , , of both oxybutynin (P