van Warmerdam L J
Department of Pharmacy, Slotervaart Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands.
Neth J Med. 1997 Jul;51(1):30-5. doi: 10.1016/s0300-2977(97)00033-8.
Dosages of anticancer agents are usually calculated from a uniform standard-the body surface area (BSA). Although the BSA is proportionate to many physiological functions, it is however only partially related to the overall drug clearance. Consequently, a wide variability in drug exposure and drug concentrations can be found between patients, by which some experience little toxicity, while others may show severe toxic symptoms. It seems clear that monitoring of plasma drug concentrations can be a useful tool to further optimize current cancer chemotherapy. The problem that pharmacokinetic parameters are usually generated from concentration-time profiles obtained after multiple venepunctures can be reduced by applying limited sampling models (LSM). Other tailor-made dosing strategies include the Calvert formula for carboplatin dosing and strategies based on the characteristics of the individual patient. It can be concluded that the determination of pharmacokinetic parameters and adjustment of the drug dose in each patient to a predefined 'target' value with an optimal therapeutic outcome, could contribute substantially to improvement of current chemotherapeutic treatment.
抗癌药物的剂量通常根据统一标准——体表面积(BSA)来计算。尽管体表面积与许多生理功能成比例,但它仅与药物的总体清除率部分相关。因此,患者之间的药物暴露和药物浓度存在很大差异,这导致一些患者几乎没有毒性反应,而另一些患者可能会出现严重的毒性症状。显然,监测血浆药物浓度可能是进一步优化当前癌症化疗的有用工具。通过应用有限采样模型(LSM),可以减少通常从多次静脉穿刺后获得的浓度-时间曲线生成药代动力学参数的问题。其他定制的给药策略包括卡铂给药的卡尔弗特公式以及基于个体患者特征的策略。可以得出结论,确定每个患者的药代动力学参数并将药物剂量调整到具有最佳治疗效果的预定义“目标”值,可极大地有助于改善当前的化疗治疗。