Pharmacokinetics, Metabolism, and Saliva Output During Transdermal and Extended-Release Oral Oxybutynin Administration in Healthy Subjects

Advantages for Transdermal over Oral Oxybutynin to Treat Overactive Bladder: Muscarinic Receptor Binding, Plasma Drug Concentration, and Salivary Secretion

“…On the other hand, little DEOB was detected in the plasma of rats receiving transdermal oxybutynin. These data indicate that transdermal application of oxybutynin produces a slow increase in the plasma concentration of oxybutynin and that this route of administration of oxybutynin efficiently avoids first-pass effect as reported in healthy subjects (Appell et al, 2003;Zobrist et al, 2003).…”

Pharmacokinetics/Pharmacodynamics Analysis of the Relationship between the in Vivo Micturition Pressure and Receptor Occupancy of (R)-Oxybutynin and Its Metabolite in Rats

“…(R/S)-OXY and (R/S)-N-desethyloxybutynin ((R/S)-DEOB), a pharmacologically active metabolite of (R/S)-OXY, inhibit muscarinic acetylcholine receptors in the bladder, especially antagonizing M 2 and M 3 receptors, which mainly mediate direct contractile response in the bladder 3) and the affinities of both compounds for M 3 receptors are higher than those for M 2 receptors. 4,5) Both (R/S)-OXY and (R/S)-DEOB have an asymmetric carbon, and the (R)-enantiomers ((R)-OXY and (R)-DEOB, respectively) have an antimuscarinic effect on the bladder smooth muscle greater than their corresponding (S)-enantiomers ((S)-OXY and (S)-DEOB, respectively).6,7) Although several reports have evaluated the relationships between PK exposure and antimuscarinic effects after the administration of (R/S)-OXY, 3,[8][9][10][11][12][13] most of them were not focused on the binding to muscarinic receptors, the competition of (R/S)-DEOB with (R/S)-OXY for the muscarinic receptor binding sites or the difference of potency between (R)-and (S)-enantiomers. In addition, there are few reports elucidating the receptor occupancy to show suitable pharmacological effects of (R)-OXY and (R)-DEOB.…”

“…6,7) Although several reports have evaluated the relationships between PK exposure and antimuscarinic effects after the administration of (R/S)-OXY, 3,[8][9][10][11][12][13] most of them were not focused on the binding to muscarinic receptors, the competition of (R/S)-DEOB with (R/S)-OXY for the muscarinic receptor binding sites or the difference of potency between (R)-and (S)-enantiomers. In addition, there are few reports elucidating the receptor occupancy to show suitable pharmacological effects of (R)-OXY and (R)-DEOB.…”

Development of oxybutynin chloride topical gel for overactive bladder

“…18 A study in healthy volunteers further showed that the ratio of N-desethyloxybutynin (N-DEO) to oxybutynin plasma exposure levels was approximately 1.3 for OXY-TDS and approximately 4.0 for orally administered extended-release oxybutynin. 19 Subsequently, it was shown that healthy subjects receiving oxybutynin via transdermal delivery had significantly greater saliva production than those who received an oral formulation. 19 An initial in vitro study evaluating different formulations of OTG suggested that skin permeation was not significantly affected by formulation strength (ie, oxybutynin concentration in the gel, Tables 1 and 2).…”

“…19 Subsequently, it was shown that healthy subjects receiving oxybutynin via transdermal delivery had significantly greater saliva production than those who received an oral formulation. 19 An initial in vitro study evaluating different formulations of OTG suggested that skin permeation was not significantly affected by formulation strength (ie, oxybutynin concentration in the gel, Tables 1 and 2). Early human studies of OTG evaluating the pharmacokinetic effects of application surface area and formulation strength found that bioavailability generally increased with decreasing formulation strength and increasing application surface area (Table 3, OG04004, OG04007; Figure 1).…”