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• W2052632290 endingPage "962" @default.
• W2052632290 startingPage "955" @default.
• W2052632290 abstract "To elucidate the relationships between the pharmacokinetics and pharmacological effects of oxybutynin ((R/S)-OXY), the micturition pressure and the plasma concentration profiles of (R)-OXY and (R)-N-desethyloxybutynin ((R)-DEOB), a pharmacologically active metabolite, after administration by three different routes (i.v., p.o. and transdermal) in rats were measured and analyzed using an inhibitory effect Emax model with their in vitro pharmacological effects. The plasma exposure ratios of (R)-DEOB to (R)-OXY calculated from the AUCs were somewhat different among the routes administered. (R)-OXY and (R)-DEOB equally inhibited the acetylcholine-induced contractions in vitro. The micturition pressure, measured using the cystometric method in vivo, exhibited saturation against the dose administered. The inhibitory effect Emax model well described the relationship between the micturition pressure and the receptor occupancy calculated from the plasma concentrations and pA2 values and resulted in an extremely small receptor occupancy (0.206%) to exhibit half of the maximum effect. The estimated receptor occupancy profiles suggested a sufficient and long-lasting receptor occupation after transdermal administration of (R/S)-OXY, while the receptor occupancy diminished rapidly after the i.v. and p.o. administration. These data indicate that transdermal administration of (R/S)-OXY would be useful to achieve suitable pharmacological effects without excess plasma concentrations." @default.
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• W2052632290 date "2007-01-01" @default.
• W2052632290 modified "2023-10-02" @default.
• W2052632290 title "Pharmacokinetics/Pharmacodynamics Analysis of the Relationship between the in Vivo Micturition Pressure and Receptor Occupancy of (R)-Oxybutynin and Its Metabolite in Rats" @default.
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• W2052632290 doi "https://doi.org/10.1248/bpb.30.955" @default.
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