Regazzi M B, Locatelli F, Buggia I, Bonetti F, Zecca M, Pregnolato M, Quaglini S
Department of Pharmacology, IRCCS Policlinico S. Matteo, Pavia, Italy.
Clin Pharmacol Ther. 1993 Jul;54(1):45-52. doi: 10.1038/clpt.1993.108.
We studied the pharmacokinetics of busulfan (16 mg/kg) in 16 pediatric patients affected by malignant and nonmalignant disorders between 6 months and 19 years of age (mean +/- SD, 5.7 +/- 6.5 years) who were undergoing allogenic (15 patients) and autologous (one patient) bone marrow transplantation. In all children, the conditioning regimen consisted of busulfan given orally at a dose of 1 mg/kg every 6 hours for 16 doses (total dose, 16 mg/kg), associated with other drugs. The pharmacokinetics of busulfan was studied during the 6-hour dosing interval on the third day of therapy by use of a high-performance liquid chromatographic assay. The value for the time to reach maximum concentration, expressed as mean +/- SD, was 1.1 +/- 0.5 hour; maximum concentration was 609.6 +/- 225.3 ng/ml; steady-state concentration was 358.9 +/- 135.5 ng/ml; area under the plasma concentration-time curve was 2153.6 +/- 813.1 ng.hr/ml; oral clearance was 0.535 +/- 0.226 L/hr/kg; and half-life was 2.4 +/- 0.8 hours. Age-related differences in busulfan disposition were observed. The mean busulfan oral clearance in a group of 10 patients with an age range from 6 months to 3 years was 0.619 L/hr/kg, whereas six patients whose ages ranged from 7 to 19 years had a oral clearance of 0.396 L/hr/kg. The half-lives for busulfan during infancy decrease continuously until early childhood but were prolonged in older children. No significant relationship between systemic exposure to busulfan and drug effect was observed.
我们研究了白消安（16毫克/千克）在16例年龄在6个月至19岁（平均±标准差，5.7±6.5岁）的患有恶性和非恶性疾病的儿科患者中的药代动力学，这些患者正在接受同种异体（15例患者）和自体（1例患者）骨髓移植。在所有儿童中，预处理方案包括每6小时口服1毫克/千克剂量的白消安，共16剂（总剂量，16毫克/千克），并联合其他药物。在治疗的第三天，通过高效液相色谱法在6小时给药间隔期间研究白消安的药代动力学。达到最大浓度的时间值，以平均±标准差表示，为1.1±0.5小时；最大浓度为609.6±225.3纳克/毫升；稳态浓度为358.9±135.5纳克/毫升；血浆浓度-时间曲线下面积为2153.6±813.1纳克·小时/毫升；口服清除率为0.535±0.226升/小时/千克；半衰期为2.4±0.8小时。观察到白消安处置存在年龄相关差异。一组年龄在6个月至3岁的10例患者的平均白消安口服清除率为0.619升/小时/千克，而年龄在7至19岁的6例患者的口服清除率为0.396升/小时/千克。婴儿期白消安的半衰期持续下降直至幼儿期，但在大龄儿童中延长。未观察到白消安全身暴露与药物效应之间的显著关系。
