Pharmacokinetics of granisetron in adults and children with malignant diseases

Granisetron (GRN) is widely used for patients with various cancers who suff er from chemotherapy-induced vomiting and nausea. The, pharmacokinetics of GRN has not been fully evaluated in such patients, however, and its dosage regimen is still controversial, In this study, we determined GRN levels in serum and urine from lung cancel patients and children suffering from cance r after intravenous infusion. In lung cancer patients, the inter-individual variations in t(1/2 beta), area under the concentration-time curve (AUC), and V-d beta were relatively smaller than expected from previous reports on healthy subjects, while t(1/2 beta), was prolonged more than 5-fold in hea lthy subjects. Urinary excretion of unchanged GRN in lung cancer patients w as ca, 15% of dose, consistent with previous reports, and one individual de monstrated an even higher urinary excretion (ca. 45%). The pharmacokinetic parameters of GRN in child cancer patients varied markedly among individual s and some child patients had smaller t(1/2 beta) than adult patients. In t hese cases, GRN should be administered at shorter intervals, These results suggested that a pharmacokinetic study of GRN was necessary for planning a dosage regimen and managing chemotherapy-induced vomiting and nausea.