中国临床药学杂志

目的研究健康志愿者单剂量和多剂量口服奥昔布宁缓释胶囊后的药动学特征,并评价奥昔布宁缓释胶囊与奥昔布宁普通片是否生物等效,为临床合理用药提供参考依据。方法20名健康志愿者分别单剂量、多剂量口服试验缓释胶囊和参比普通片剂,于规定时间点取血,以LC-MS联用法测定奥昔布宁血药浓度,采用3P97软件计算各制剂单剂量和多剂量给药后的药动学参数。结果单剂量给药,奥昔布宁缓释胶囊和普通片的ρ_max分别为(8.27±7.28)μg·L^-1和(17.16±12.17)μg·L^-1;t_max分别为(2.55±0.85)h和(0.82±0.35)h;t(?)分别为(6.23±2.78)h和(5.54±2.18)h;AUC_?分别为(51.94±40.27)μg·h·L^-1和(49.84±34.33)μg·h·L^-1;AUC_?分别为(57.25±40.78)μg·h·L^-1和(54.68±36.44)μg·h·L^-1。奥昔布宁缓释胶囊相对于普通片生物利用度F_?为(104.15±15.47)%。多剂量给药,奥昔布宁缓释胶囊和普通片的ρ_max^ss分别为(24.00±10.41)μg·L^-1和(15.37±8.00)μg·L^-1;ρ_min^ss分别为(1.59±0.80)μg·L^-1和(1.33±0.80)μg·L^-1;ρ_av^ss分别为(5.01±2.22)μg·L^-1和(2.49±1.17)μg·L^-1;AUC^ss分别为(120.19±53.24)μg·h·L^-1和(59.85±28.01)μg·h·L^-1;DF分别为(446.23±135.27)%和(579.75±148.10)%;奥昔布宁缓释胶囊波动度明显小于普通片。结论试验制剂具有缓释作用。试验制剂与参比制剂的ρ_max生物不等效,但AUC_?生物等效。

AIM To study the pharmacokinetics and bioequivalence of oxybutynin sustained-release capsule and conventional tablet in healthy volunteers.METHODS Twenty healthy male volunteers were given oxybutynin in single and multiple doses in this experiment.A HPLC-MS method was applied to determine the serum concentration of oxybu- tynin,the pharmacokinetic parameters and bioequivalence were evaluated by program 3P97.RESULTS Theρ_max,t_max, t(?),AUC_?and AUC_?of oxybutynin sustained-release capsule and conventional tablet from the single-dose study were as follows:(8.27±7.28)μg·L^-1and(17.16±12.17)μg·L^-1,(2.55±0.85)h and(0.82±0.35)h,(6.23±2.78)h and(5.54±2.18)h,(51.94±40.27)μg·h·L^-1and(49.84±34.33)μg·h·L^-1,(57.25±40.78)μg·h·L^-1and(54.68±36.44)μg·h·L^-1.The maximum serum concentration of sustained-release capsule was decreased, the relative bioavailability of single oral sustained-release capsule to conventional tablet F_?was(104.15±15.47)%. The pharmacokinetic parameters of oxybutynin sustained-release capsule and conventional tablet after multiple dose were as follows:ρ_max^sswere(24.00±10.41)μg·L^-1and(15.37±8.00)μg·L^-1respectively;ρ_min^sswere(1.59±0.80)μg·L^-1and(1.33±0.80)μg·L^-1respectively;ρ_av^sswere(5.01±2.22)μg·L^-1and(2.49±1.17)μg·L^-1respectively; AUC^sswere(120.19±53.24)μg·h·L^-1and(59.85±28.01)μg·h·L^-1respectively;DF were(446.23±135.27)% and(579.75±148.10)% respectively.The mean DF of multiple dose sustained-release capsule was lower than that of conventional tablet.CONCLUSION The sustained-release capsules are extendedly released.The test and reference preparations are bioequivalent for AUC_?,but not bioequivalent forρ_max.