BAYESIAN-ESTIMATION OF ETOPOSIDE PHARMACO KINETIC PARAMETERS

Studies of the relationships between the pharmacokinetics of a drug an d its pharmacodynamics could significantly improve chemotherapy effica cy. However, despite their proven value pharmacokinetic studies someti mes appear as cumbersome and difficult procedures. The bayesian approa ch associated with an optimal sampling time strategy (OST) allows the determination of the pharmacokinetic parameters of a drug with a small er number of blood samples compared with that required by the classic maximum likelihood estimation (MLE). Therefore, the bayesian approach may lead to a less discomfort to the patients and less work for the me dical staff. Such a method was developed to determine the individual p harmacokinetic parameters of etoposide (VP16). First, the statistical characteristics of the pharmacokinetic parameters were evaluated in 14 courses from 14 patients. Then, based on these results, a three-sampl e strategy was developed. Validation of this methodology was performed in 7 new patients and evaluated by computing bias and precision. The performance of the developed methodology shows that it could successfu lly be applied for the determination of VP16 pharmacokinetic parameter s.