Figure 2. Mean steady state (±SD) R-oxybutynin plasma concentrations following administration of 5 to 20 mg DITROPAN XL once daily in children aged 5-15. Plot represents all available data normalized to an equivalent of DITROPAN XL 5 mg once daily.

Food Effects

The rate and extent of absorption and metabolism of oxybutynin are similar under fed and fasted conditions.

Distribution

Plasma concentrations of oxybutynin decline biexponentially following intravenous or oral administration. The volume of distribution is 193 L after intravenous administration of 5 mg oxybutynin chloride.

Metabolism

Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4 found mostly in the liver and gut wall. Its metabolic products include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and desethyloxybutynin, which is pharmacologically active. Following DITROPAN XL administration, plasma concentrations of R- and S-desethyloxybutynin are 73% and 92%, respectively, of concentrations observed with oxybutynin.

Excretion

Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Also, less than 0.1% of the administered dose is excreted as the metabolite desethyloxybutynin.

Dose Proportionality

Pharmacokinetic parameters of oxybutynin and desethyloxybutynin (Cmax and AUC) following administration of 5-20 mg of DITROPAN XL are dose proportional.

Special Populations

Geriatric

The pharmacokinetics of DITROPAN XL were similar in all patients studied (up to 78 years of age).

Pediatric

The pharmacokinetics of DITROPAN XL were evaluated in 19 children aged 5-15 years with detrusor overactivity associated with a neurological condition (e.g., spina bifida). The pharmacokinetics of DITROPAN XL in these pediatric patients were consistent with those reported for adults (see Tables 1 and 2, and Figures 1 and 2 above).

Gender

There are no significant differences in the pharmacokinetics of oxybutynin in healthy male and female volunteers following administration of DITROPAN XL.

Race

Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on race in healthy volunteers following administration of DITROPAN XL.

Renal Insufficiency

There is no experience with the use of DITROPAN XL in patients with renal insufficiency.

Hepatic Insufficiency

There is no experience with the use of DITROPAN XL in patients with hepatic insufficiency.

Drug-Drug Interactions:

See PRECAUTIONS: DRUG INTERACTIONS

Clinical Studies

DITROPAN XL® (oxybutynin chloride) was evaluated for the treatment of patients with overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in three controlled studies and one open label study. The majority of patients were Caucasian (89.0%) and female (91.9%) with a mean age of 59 years (range, 18 to 98 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge) as evidenced by ≥ 6 urge incontinence episodes per week and ≥ 10 micturitions per day. Study 1 was a fixed dose escalation design, whereas the other studies used a dose adjustment design in which each patient's final dose was adjusted to a balance between improvement of incontinence symptoms and tolerability of side effects. Controlled studies included patients known to be responsive to oxybutynin or other anticholinergic medications, and these patients were maintained on a final dose for up to 2 weeks.

The efficacy results for the three controlled trials are presented in the following tables and figures.

Number of Urge Urinary Incontinence Episodes Per Week

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