Pharmacokinetics of the R- and S-Enantiomers of Oxybutynin and N-Desethyloxybutynin Following Oral and Transdermal Administration of the Racemate in Healthy Volunteers

• Published in: Pharmaceutical research Vol. 18; no. 7; pp. 1029 - 1034
• Main Authors: Zobrist, R. Howard, Schmid, Bernhard, Feick, Alexander, Quan, Danyi, Sanders, Steven W.
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.07.2001; Springer Nature B.V
• Subjects: Administration, Cutaneous; Administration, Oral; Adult; Biological and medical sciences; Cross-Over Studies; Female; Humans; Male; Mandelic Acids - administration & dosage; Mandelic Acids - blood; Mandelic Acids - pharmacokinetics; Medical sciences; Middle Aged; Muscle; Parasympatholytics - administration & dosage; Parasympatholytics - blood; Parasympatholytics - pharmacokinetics; Pharmacology. Drug treatments; Skin Absorption - physiology; Stereoisomerism; Human; Oral administration; Metabolism; Normal; In vitro; Percutaneous route; In vivo; Randomization; Absorption; Antispasmodic agent; Enantiomer; Oxybutynin; Pharmacokinetics
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1010956832113

To characterize the enantiomers of oxybutynin (OXY) and N-desethyloxybutynin (DEO) following transdermal and oral administration. OXY was administered either as a single transdermal system over a 96 h wear period or as a single 5 mg immediate-release tablet to 18 healthy male and female subjects in a randomized, open-label, two-way crossover design. Blood samples were collected for 108 h after application of the transdermal system and for 6 h after oral administration. Plasma concentrations of the R- and S-enantiomers of OXY and DEO were assayed by LC-MS/MS. Enantiomer in vitro skin flux was evaluated using human cadaver skin. In vitro skin flux studies demonstrated equal absorption of R and S- OXY. Plasma concentrations and pharmacokinetic parameters of the R-enantiomers of OXY and DEO were slightly lower than the S-enantiomers following transdermal OXY. The relative AUC values were S-OXY>S-DEO>R-OXY>R-DEO. The AUC ratios of DEO/ OXY were less than 1 for both the R- and S- enantiomers. Following oral dosing, plasma DEO concentrations greatly exceeded OXY resulting in relative AUC values of R-DEO>S-DEO>S-OXY>R-OXY. The mean AUC ratios of S- and R-DEO/OXY were 3.25 and 8.93, respectively. Stereoselective metabolism of OXY was evident following both transdermal and oral administration of OXY. The reduced pre-systemic metabolism of transdermally administered OXY compared to oral administration resulted in not only significantly lower DEO plasma concentrations, but also a different metabolite pattern. The differences between R-OXY and R-DEO following the two routes of administration support the potential for comparable clinical efficacy and reduced anticholinergic side-effects with transdermal treatment.