A Simple Dosing Scheme for Intravenous Busulfan Based on Retrospective Population Pharmacokinetic Analysis in Korean Patients

• DOI: 10.4196/kjpp.2012.16.4.273
• Publication Date: 2012-08-13T04:33:16Z
• Authors: Sangmin Choe; Gayeong Kim; Hyeong-Seok Lim; Sang-Heon Cho; Jong-Lyul Ghim; Jin Ah Jung; Un-Jib Kim; Gyujeong Noh; Kyun-Seop Bae; Dongho Lee
• Keywords: NONMEM

Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of prospective randomized trial for comparison four-times daily versus once-daily intravenous busulfan was carried out to search predictive factors (iBu) pharmacokinetics (PK). In this study the PK iBu characterized provide suitable dosing recommendations. Patients were receive iBu, either as 0.8 mg/kg every 6 h or 3.2 over 4 days prior hematopoietic stem cell transplantation. total, 295 concentrations analyzed NONMEM. Actual body weight and sex significant covariates affecting iBu. Sixty patients included in (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates typical patient weighing 65 kg were: clearance (CL) 7.6 l/h volume distribution (V(d)) 32.2 l men 29.1 L women. Inter-individual random variabilities CL V(d) 16% 9%. Based on estimate from final model, simple dosage scheme achieve target AUC(0-inf) (defined median dosage) 26.18 mg/l·hr, proposed: 24.79·ABW(0.5) mg q24h, where ABW represents actual kilograms. The reduced unexplained interindividual Vd being covariate iBU. We propose new based only ABW.