Background: We investigated the pharmacokinetics of etoposide (ETP) to reduce the inter-individual variations of ETP\nconcentrations in patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation.\nWe also carried out an in vivo study using rats to verify the dose adjustment.\nMethods: This study included 20 adult patients. ETP was administered intravenously at a dose of 15 mg/kg once\ndaily for 2 days (total dose: 30 mg/kg) combined with standard conditioning of cyclophosphamide and total body\nirradiation. In an in vivo study using rats, ETP was administered intravenously at a dose of 15 mg/kg or an adjusted\ndose. The ETP plasma concentration was determined by using HPLC. The pharmacokinetic parameters were estimated\nby using a 1-compartment model.\nResults: The peak concentration (Cmax) of ETP and the area under the plasma concentration-time curve (AUC) of ETP\ndiffered greatly among patients (range of Cmax, 51.8 - 116.5 �¼g/mL; range of AUC, 870 - 2015 �¼g �· h/mL). A significant\nrelationship was found between Cmax and AUC (R = 0.85, P < 0.05). Distribution volume (Vd) was suggested to be one\nof the factors of inter-individual variation in plasma concentration of ETP in patients (range of Vd, 0.13 - 0.27 L/kg), and\ncorrelated with Alb and body weight (R = 0.56, P < 0.05; R = 0.40, P < 0.05 respectively). We predicted Vd of rats by body\nweight of rats (with normal albumin levels and renal function), and the dose of ETP was adjusted using predicted Vd.\nIn the dose adjustment group, the target plasma ETP concentration was achieved and the variation of plasma ETP\nconcentration was decreased.\nConclusion: The results suggested that inter-individual variation of plasma concentration of ETP could be reduced by\npredicting Vd. Prediction of Vd is effective for reducing individual variation of ETP concentration and might enable a\ngood therapeutic effect to be achieved.
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