1. Dolasetron (Anzemet®) is apotent andselective 5-HT₃ receptor antagonist which is rapidly and extensively reduced to yield its major pharmacologically active metabolite, reduced dolasetron (RD). RD is further metabolized by CYP450 enzymes as well as undergoing renal excretion. As both in vitro and in vivo data on RD were available from animals andman, two approaches to predict the human pharmacokinetic parameters ofRD were assessed. 2. First, in vitro studies, using liver microsomes from animal species and man, were undertaken to measure V_max and K_m and to assess the intrinsic clearance (CL_int). With appropriate liver weight and liver bloodflow scaling factorsthe predicted in vivo metabolic clearance (CL_{m_pred}) was calculated. Human CL_{m_pred} was underestimated by a factor of 5 when it was calculated using the above scaling factors. As, in a prospective study, the observed human in vivo metabolic clearance (CL_{m_obs})is unknown, CL_{m_pred} was substituted into the least-squares correlation equation obtained from a plot of CL_{m_pred} against CL_{m_obs}, using animal data. The estimate of human CL_{m_obs} was improved as it was only underestimated by a factor of 1.5. 3. Second, allometric scaling of in vivo animal pharmacokinetic data, using body weight, was performed topredict pharmacokinetic parameters in man. Good predictions of human pharmacokinetic parameters of RD were obtained for plasma clearance (1.7 l/min predicted versus 1.6 l/min observed), half-life (6.0 h predicted versus 5.6 h observed), and volume of distribution (860.9 l predicted versus 770.4 l observed). 4. The integration of in vitro metabolic data from microsomes gave similar results to conventional allometric scaling, whereas the normalization of clearance by brain weight resulted in an approximately three-fold underestimation of human clearance. 5. For RD, a drug that is eliminated by both renal and metabolic clearance, retrospective conventional allometric scaling allowed accurate prediction of pharmacokinetic parameters in man, whereas in vitro-in vivo scaling resulted in an underestimation of in vivo CL_m. Although these results are somewhat at variance, ideally both scaling methods should be applied to improve the prediction of human pharmacokinetic parameters.