The pharmacokinetics of oxybutynin in man

Abstract

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.

Update on the management of overactive bladder: patient considerations and adherence

“…30 A percentage of the parent drug is converted to the active metabolite N-desethyloxybutynin (N-DEO) before reaching the bladder or the salivary glands, bowel, eye, and brain, the other organs primarily responsible for side effects. 31 N-DEO has pharmacological activity on the human detrusor muscle that is similar to that of oxybutynin during in vitro studies. The N-DEO to oxybutynin ratio in oxybutynin IR is ∼5.5:1.…”

Development of a Novel Simplified PBPK Absorption Model to Explain the Higher Relative Bioavailability of the OROS® Formulation of Oxybutynin

“…1a. The model is comprised of two anatomically defined compartments, systemic blood and liver, and three additional empirical tissue compartments, necessary to describe OXY's disposition after an intravenous (IV) infusion (30). All of the aforementioned compartments were assumed to be well-mixed, where drug transport into and from the tissues was assumed to occur by means of perfusion-limited processes.…”

“…2 (blood) was later expressed as plasma concentration by dividing C blood by the blood to plasma ratio (BP). OXY's systemic elimination was assumed to occur exclusively through hepatic metabolism, given that only less than 0.02% of the administered dose was found unchanged in the urine after IV administration (30). The dynamics of the liver compartment were described by Eq.…”

“…OXY is a highly permeable and soluble compound (BCS Class 1) (21). After oral administration, OXY is rapidly absorbed and undergoes extensive first-pass metabolism in both the intestinal wall and the liver, mainly mediated by CYP3A4 (28)(29)(30). When formulated as a once a day (MR) OROS® formulation, the relative bioavailability of OXY was around 153% compared to its IR tablet, while the exposure of its main metabolite, Ndesethyloxybutynin (DEOB) was reduced by almost 30% (28).…”

Inhibition of airway hyperreactivity by oxybutynin chloride in subjects with cervical spinal cord injury

“…1,2 Pharmacological action, as assessed in animal studies involving the gastro-intestinal tract, uterus, seminal vesicle, bladder and detrusor, has been attributed to direct potent musculotropic antispasmodic action, probably re¯ecting a combination of local anesthetic properties and moderate anticholinergic and antihistamine activity. 1,3,4 In a study of pulmonary eects, pretreatment of conscious guinea pigs with subcutaneous oxybutynin blocked carbachol-induced, respiratory-associated generalized collapse, and pretreatment by intravenous administration in anesthetized animals inhibited methacholine-induced bronchoconstriction. 5 Whether oxybutynin causes relaxation of human airway smooth muscle or attenuates experimentally-induced bronchoconstriction has not been determined.…”