Ditropan XL - Clinical Pharmacology

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DITROPAN XL steady-state pharmacokinetics was studied in 19 children aged 5-15 years with detrusor overactivity associated with a neurological condition (e. g. spina bifida). The children were on DITROPAN XL total daily dose ranging from 5 to 20 mg (0.10 to 0.77 mg/ kg). Sparse sampling technique was used to obtain serum samples. When all available data are normalized to an equivalent of 5 mg per day Ditropan XL, the mean pharmacokinetic parameters derived for R-and S-oxybutynin and R-and S-desethyloxybutynin are summarized in Table 2. The plasma-time concentration profiles for R-and S-oxybutynin are similar in shape; Figure 2 shows the profile for R-oxybutynin when all available data are normalized to an equivalent of 5 mg per day.

Table 2 Mean ± SD R-and S-Oxybutynin and R-and S-Desethyloxybutynin Pharmacokinetic Parameters in Children Aged 5-15 Following Administration of 5 to 20 mg DITROPAN XL Once Daily (n= 19)

All Available Data Normalized to an Equivalent of DITROPAN XL 5 mg Once Daily

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.