논문/저서
| A simple dosing scheme for intravenous busulfan based on retrospective population pharmacokinetic analysis in korean patients. | ||
|---|---|---|
|
Korean J Physiol Pharmacol. 2012 Aug;16(4):273-80. doi: 10.4196/kjpp.2012.16.4.273. Epub 2012 Aug 10. A simple dosing scheme for intravenous busulfan based on retrospective population pharmacokinetic analysis in korean patients. Choe S, Kim G, Lim HS, Cho SH, Ghim JL, Jung JA, Kim UJ, Noh G, Bae KS, Lee D.
Abstract Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosingrecommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (V(d)) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and V(d) were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target AUC(0-inf) (defined as median AUC(0-inf) with a once-daily dosage) of 26.18 mg/l·hr, was proposed: 24.79·ABW(0.5) mg q24h, where ABW represents the actual body weight in kilograms. The dosingscheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.
KEYWORDS: Dosage scheme; Intravenous busulfan; Population pharmacokinetics
PMID: 22915993 PMCID: PMC3419763 DOI: 10.4196/kjpp.2012.16.4.273
|
||
- 이전글
- A single-dose, crossover study comparing the pharmacokinetics and pharmacodynamics of 2 formulations of metformin in healthy volunteers.
- 다음글
- Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers.
