El-Yazigi A, Sawchuk R J
J Pharm Sci. 1981 Apr;70(4):452-6. doi: 10.1002/jps.2600700429.
Theophylline pharmacokinetics following oral and intravenous administration were studied, and the absolute bioavailability of five commercially available products was determined using the rabbit as an in vivo model. Concentration-dependent clearance studies were performed by multiple constant-rate infusion and multiple bolus dose administration of aminophylline. Theophylline pharmacokinetics following the oral administration of these products obeyed the one-compartment open model adequately. However, the data obtained following rapid intravenous aminophylline administration in the rabbit fit either the one-compartment model (half-life = 2.8 hr and the volume of distribution = 4.4 hr and Vd(beta) = 0.708 liter/kg). There were no significant product-to-product differences in the time to peak (tmax), the rate constant of absorption (ka), or the percent of dose absorbed at 1 hr (F1); however, differences in the absolute bioavailability (F), dose-normalized peak serum concentration (Cmax(n)), and percent of dose absorbed at 6 hr (F6) were significant. There was no evidence of concentration-dependent clearance for theophylline in the rabbit in the serum concentration range studied, but the results of the multiple constant-rate infusion study suggest that total clearance decreases at higher serum theophylline concentrations.
研究了口服和静脉注射后茶碱的药代动力学，并以兔作为体内模型测定了五种市售产品的绝对生物利用度。通过氨茶碱的多次恒速输注和多次推注给药进行浓度依赖性清除率研究。口服这些产品后茶碱的药代动力学充分符合单室开放模型。然而，在兔中快速静脉注射氨茶碱后获得的数据符合单室模型（半衰期 = 2.8小时，分布容积 = 4.4小时，β相分布容积 = 0.708升/千克）。在达峰时间（tmax）、吸收速率常数（ka）或1小时吸收剂量百分比（F1）方面，产品之间没有显著差异；然而，绝对生物利用度（F）、剂量标准化的血清峰浓度（Cmax(n)）和6小时吸收剂量百分比（F6）存在显著差异。在所研究的血清浓度范围内，兔体内茶碱没有浓度依赖性清除的证据，但多次恒速输注研究结果表明，在较高的血清茶碱浓度下总清除率会降低。
