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

  title={Pharmacokinetics of the R- and S-Enantiomers of Oxybutynin and N-Desethyloxybutynin Following Oral and Transdermal Administration of the Racemate in Healthy Volunteers},
  author={R. Howard Zobrist and Bernhard Schmid and Alexander Feick and Danyi Quan and Steven W. Sanders},
  journal={Pharmaceutical Research},
AbstractPurpose. To characterize the enantiomers of oxybutynin (OXY) and N-desethyloxybutynin (DEO) following transdermal and oral administration. Methods. 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… 

Stereoselective pharmacokinetics of oxybutynin and N-desethyloxybutynin in vitro and in vivo

Data indicate that for the stereoselectivity of OXY, the unbound fraction of each OXY enantiomer was a major factor and the metabolism in liver had a minimal effect.

Pharmacokinetics and Metabolism of Transdermal Oxybutynin: In Vitro and in Vivo Performance of a Novel Delivery System

Sustained delivery over 4 days and multiple sites allow a convenient, well-tolerated, twice-weekly OXY TDS dosing and the consistent delivery, absorption, and pharmacokinetics should result in an effective treatment of patients with overactive bladder.

A Population Pharmacokinetic Model of (R)‐ and (S‐) Oxybutynin and Its Active Metabolites After Oral and Intravesical Administration to Healthy Volunteers

Pharmacokinetic simulations suggest that exposure for 12.5 mg (R)‐oxybutynin administered twice daily might not compromise efficacy and tolerability compared with exposure for standard thrice‐daily administrations, and this assumption needs to be assessed in clinical studies.

Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oral oxybutynin administration in healthy subjects.

Lower N-desethyloxybutynin plasma concentration and greater saliva output during transdermal treatment correspond to the reported low incidence of dry mouth in patients with overactive bladder and minimizes metabolism to N- Desethyloxy butynin compared with extended-release oral administration.

New insights in the metabolism of oxybutynin: evidence of N-oxidation of propargylamine moiety and rearrangement to enaminoketone

The oxidative metabolic fate of oxybutynin was revisited by liquid chromatography–tandem mass spectrometry analysis of incubations with rat and human liver fractions, and by measuring plasma and urine samples collected after oral administration of oxy butynin in rats, highlighting that not only N-deethylation but also N-oxidation participates in the clearance of oxy Butynin after oraladministration.

Pharmacokinetics of Oxybutynin Chloride Topical Gel

The bioavailability of oxybutynin and its pharmacokinetic profile are not greatly affected by application site selection, post-application showering or sunscreen use shortly before or after dosing with OTG.

Enhancement effects of (R) and (S) enantiomers and the racemate of a model enhancer on permeation of theophylline through human skin

It was shown that there was no difference in the permeation enhancement ability between the (R)-(–) and (S)-(+) isomers of 6-aminohexanoic acid 2-octylester, suggesting that the enhancing properties of the compounds are not dependent on their spatial arrangement.

Transdermal Oxybutynin

Significant reductions in incontinence episodes following transdermal oxybutynin treatment were observed and the clinical efficacy was similar to that of oral tolterodine or oral oxy butynin, which was well tolerated in clinical trials.



Enantioselective disposition of salbutamol in man following oral and intravenous administration.

The active (-)R enantiomers of salbutamol undergoes significantly faster metabolism in man than the inactive (+)S enantiomer resulting in considerably lower bioavailability of the active enantiome following oral administration.

Measurement of oxybutynin and its N-desethyl metabolite in plasma, and its application to pharmacokinetic studies in young, elderly and frail elderly volunteers.

Results indicate that for frail elderly patients a lower initial starting dose of 2.5 mg OB given two or three times a day may provide adequate therapeutic blood levels of the drug.

Enantiomers of oxybutynin: in vitro pharmacological characterization at M1, M2 and M3 muscarinic receptors and in vivo effects on urinary bladder contraction, mydriasis and salivary secretion in guinea pigs.

(R)OXY may offer no significant pharmacological advantage over (R/S)O XY in terms of its principal therapeutic and side effect profile, and it appears that (R)/S OXY resides predominantly in the (R)-enantiomer.

The pharmacokinetics of oxybutynin in man

The low absolute systemic availability of oxybutynin, the large interindividual variability in its plasma concentrations, and the apparent absence of intact oxy butynin in the urine suggest that its major pathway of elimination is hepatic metabolism.

Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects.

Stereoselectivity in the first pass metabolism of nitrendipine exhibited little intersubject variability and therefore is not a major factor in the wide variability in systemic availability of the more-potent (S)-enantiomer.

Comparison of the antimuscarinic and antispasmodic actions of racemic oxybutynin and desethyloxybutynin and their enantiomers with those of racemic terodiline.

S-oxybutynin deserves consideration for development as a single-enantiomer drug for the treatment of urinary incontinence but, like RS-terodiline, produce a lower incidence of antimuscarinic side-effects than seen with RS-oxy butynin.

R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine.

Stereoselectivity was observed for Ca++-channel antagonism, spasmolytic and local anesthetic properties of (R/S)OXY and its enantiomers, but no stereoselective effects were observed forCa++- channel antagonistic and spasmsolytic effects of (Oxybutynin)Oxy butynin.

The pharmacokinetics of intravesical and oral oxybutynin chloride.

The treatment of detrusor instability in postinenopausal women with oxybutynin chloride: a double blind placebo controlled study

Because such contractions were abolished by placebo in six of sevcn patients, Tapp et ul.