Powis G, Ames M M, Kovach J S
Cancer Chemother Pharmacol. 1981;6(1):1-9. doi: 10.1007/BF00253003.
Dose-dependent pharmacokinetics have been reported more frequently for anticancer drugs than for other drugs, probably because anticancer drugs are studied over a wide range of doses during early evaluation and because of the increasing use of anticancer drugs at very high doses. Dose-dependent pharmacokinetics are reflected most commonly as an increase in the biological half-life of a drug and a greater than proportional increase in plasma concentration of the drug and in area under the drug concentration-time curve with increase in dose. Occasionally the rate of drug removal increases with increasing dose. These nonlinear changes in drug concentrations with dose may lead to increases in toxicity out of proportion to increases in dose. Appreciation of the possibility of dose-dependent pharmacokinetics is important in the clinical pharmacologic evaluation of new drugs, and may be essential for the design of effective therapeutic regimens.
与其他药物相比，抗癌药物的剂量依赖性药代动力学报道更为频繁，这可能是因为在早期评估中抗癌药物在广泛的剂量范围内进行研究，并且由于高剂量抗癌药物的使用日益增加。剂量依赖性药代动力学最常见的表现是药物生物半衰期延长，药物血浆浓度和药物浓度-时间曲线下面积随剂量增加呈超比例增加。偶尔，药物清除率也会随剂量增加而增加。药物浓度随剂量的这些非线性变化可能导致毒性增加与剂量增加不成比例。认识到剂量依赖性药代动力学的可能性在新药的临床药理学评估中很重要，对于有效治疗方案的设计可能至关重要。
