Factors Affecting the Pharmacokinetics of CPT-11: The Body Mass Index, Age and Sex are Independent Predictors of Pharmacokinetic Parameters of CPT-11

This study was conducted to describe the relationshipbetween pharmacokinetics of CPT-11 and its active metaboliteSN-38, and clinical values with special emphasis on theinfluence of relative weight referring to the appropriatenessof a conventional dose adjustment method by body surface area(BSA). Thirty-six patients received 100 mg/m2ofCPT-11 intravenously over 90 min. Body Mass Index (BMI) wasused as a measure of relative weight which is calculated fromthe equation: BMI=weight(kg)/[height(m)]2. Thearea under the concentration-time curve (AUC) of CPT-11 wassignificantly correlated with sex, age, poorer creatinineclearance and indocyanine green retention test (ICG). Thepeak plasma concentration (Cmax) of CPT-11 was significantlycorrelated with sex a larger BMI, BSA and age. The AUC ofSN-38 was significantly correlated with ICG. The volume ofdistribution at steady state of CPT-11 inversely correlatedwith BMI. Multiple regression analysis revealed that the bestfitting model with significant independent predictors for AUCof CPT-11 included age and sex (F=6.93, R2=0.29).That of Cmax of CPT-11 included sex and BMI (F=8.96,R2=0.35). The only independent predictor of AUC ofSN-38 was ICG (F=7.75, R2=0.19). These resultsindicated that several factors affect pharmacologicalbehaviors of CPT-11 even in patients with normal organfunctions. The dose modification method based solely on BSA isnot sufficient to reduce interpatient variability of cancerchemotherapy. The influence of relative weight, sex and age onpharmacokinetics/pharmacodynamics should be taken intoconsideration in every pharmacological approach to establishthe ideal dose modification method.