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

@article{Zobrist2004PharmacokineticsOT,
  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},
  year={2004},
  volume={18},
  pages={1029-1034}
}
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… Expand
Stereoselective pharmacokinetics of oxybutynin and N-desethyloxybutynin in vitro and in vivo
TLDR
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. Expand
Pharmacokinetics and Metabolism of Transdermal Oxybutynin: In Vitro and in Vivo Performance of a Novel Delivery System
TLDR
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. Expand
A Population Pharmacokinetic Model of (R)‐ and (S‐) Oxybutynin and Its Active Metabolites After Oral and Intravesical Administration to Healthy Volunteers
TLDR
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. Expand
Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oral oxybutynin administration in healthy subjects.
TLDR
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. Expand
Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: results of an open label, randomized, prospective clinical study.
TLDR
Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity. Expand
Parallel achiral-chiral determination of oxybutynin, N-desethyl oxybutynin and their enantiomers in human plasma by LC-MS/MS to support a bioequivalence trial.
TLDR
The pharmacokinetic profiles showed that the plasma concentration of (R)-oxy butynin was lower than that of (S)-oxybutynin, while a reverse trend was observed for the enantiomers of N-desethyl oxybutyn in. Expand
New insights in the metabolism of oxybutynin: evidence of N-oxidation of propargylamine moiety and rearrangement to enaminoketone
TLDR
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. Expand
Pharmacokinetics of Oxybutynin Chloride Topical Gel
TLDR
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. Expand
Enhancement effects of (R) and (S) enantiomers and the racemate of a model enhancer on permeation of theophylline through human skin
TLDR
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. Expand
Transdermal Oxybutynin
TLDR
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. Expand
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