Piotrovskij V K, Paintaud G, Alván G, Trnovec T
Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
Pharm Res. 1994 Sep;11(9):1346-51. doi: 10.1023/a:1018911032009.
Amoxicillin pharmacokinetics was modeled using a two-compartment disposition model and a saturable time-constrained absorption model with a storage compartment. The absorption model parameters estimated by the nonlinear regression are: a rate constant of the systemic input, ksys, (median: 1.31 h-1, range: 0.79-7.01 h-1), a maximal absorption rate, Vmax (median: 1407 mg/h, range: 703-4181 mg/h), an account corresponding to the half maximal rate, Kma, (median: 1077 mg, range: 235-4376 mg), time of the absorption cessation, Tabs, (median: 1.72 h, range: 0.82-4.53 h) and absorption lag time. Tlag, (median: 0.085 h, range: 0-0.123 h). It was shown, that the first-order absorption parallel to the saturable process is negligible in the dose range studied. The model described well the dependence of areas under concentration-time curves on the dose determined in several earlier studies. It was used also to predict the fraction of the amoxicillin dose absorbed for different doses. Simulations performed over a wide dose range (50-10000 mg) demonstrated that the fraction absorbed decreases nonlinearly from 90% at 50 mg to 22% at 10000 mg and strongly depends on the duration of the absorption period.
阿莫西林的药代动力学采用二室处置模型和带有储存室的饱和时间限制吸收模型进行建模。通过非线性回归估计的吸收模型参数为：全身输入速率常数ksys（中位数：1.31 h-1，范围：0.79 - 7.01 h-1）、最大吸收速率Vmax（中位数：1407 mg/h，范围：703 - 4181 mg/h）、对应于半最大速率的量Kma（中位数：1077 mg，范围：235 - 4376 mg）、吸收停止时间Tabs（中位数：1.72 h，范围：0.82 - 4.53 h）以及吸收滞后时间Tlag（中位数：0.085 h，范围：0 - 0.123 h）。结果表明，在所研究的剂量范围内，与饱和过程平行的一级吸收可忽略不计。该模型很好地描述了在先前几项研究中确定的浓度 - 时间曲线下面积对剂量的依赖性。它还用于预测不同剂量阿莫西林吸收剂量的分数。在50 - 10000 mg的宽剂量范围内进行的模拟表明，吸收分数从50 mg时的90%非线性下降至10000 mg时的22%，并且强烈依赖于吸收期的持续时间。
