DEVELOPMENT OF A LIMITED SAMPLING APPROACH IN PHARMACOKINETIC STUDIES- EXPERIENCE WITH THE ANTIEPILEPSY DRUG TIAGABINE

A sparse sampling method is proposed to assess pharmacokinetic paramet ers after a single dose of the antiepilepsy drug tiagabine. Pharmacoki netic parameters obtained from two different pharmacokinetic studies w ere compared using sparse sampling (7 blood samples) with extensive sa mpling (15 to 16 blood samples). The results indicated that sparse blo od samples taken at appropriate times can be used to estimate pharmaco kinetic parameters as accurately as extensive blood samples. In additi on, a limited sampling model (LSM) was developed using samples fram 10 subjects at two time points (6 and 8 hours). The model was validated in 40 subjects and provided good population mean estimates of area und er the concentration-time curve (AUC) and maximum concentration (C-max ). The sparse sampling method described here can be used to assess pha rmacokinetic parameters in drug development provided a prior knowledge of the pharmacokinetics of a drug has been obtained front extensive s ampling. Further, the LSM described here may be useful in estimating A UC and C-max of tiagabine using two samples in clinical settings. The LSM approach described here can also be used to estimate AUC and C-max of a drug in preclinical toxicokinetic studies without detailed pharm acokinetic studies. (C)1998 The American College of Clinical Pharmacol ogy.