Poonkuzhali B, Srivastava A, Quernin M H, Dennison D, Aigrain E J, Kanagasabapathy A S, Krishnamoorthy R, Chandy M
Department of Hematology, Christian Medical College and Hospital, Vellore, Nadu, India.
Bone Marrow Transplant. 1999 Jul;24(1):5-11. doi: 10.1038/sj.bmt.1701814.
The pharmacokinetics of busulphan were studied in 23 thalassaemic children undergoing BMT. Patients received busulphan at a dose of either 16 mg/kg with cyclophosphamide and ATG (Group A) or 600 mg/m2 (with cyclophosphamide alone) (Group B) in 16 divided doses every 6 h over 4 days. Busulphan levels were analyzed by a modified GC-MS method. The dose of busulphan/kg for patients in group B was 64% (range 56-71%) higher than that for patients in group A. The mean AUC, Css, Cmax and MRV were significantly higher in group B as compared with group A for both doses 1 and 13. There was no significant difference in Vd/F, T1/2 and Kel between the two groups. A significant decrease in AUC and Css was found between 1st and 13th doses in group B, but not in group A. The Cl/F values in group A were significantly higher than those in group B after dose 1, but not after dose 13. No increase in toxicity due to the higher dose of busulphan was noted. We conclude that busulphan at 600 mg/m2 results in much higher systemic exposure to the drug as compared to 16 mg/kg, without increase in toxicity in children with beta thalassaemia major.
对23名接受骨髓移植的地中海贫血儿童的白消安药代动力学进行了研究。患者接受白消安治疗，A组剂量为16mg/kg，同时使用环磷酰胺和抗胸腺细胞球蛋白；B组剂量为600mg/m²（仅使用环磷酰胺），在4天内每6小时分16次给药。采用改良的气相色谱-质谱法分析白消安水平。B组患者每千克白消安剂量比A组高64%（范围56 - 71%）。对于剂量1和13，B组的平均AUC、Css、Cmax和MRV均显著高于A组。两组间的Vd/F、T1/2和Kel无显著差异。B组第1剂和第13剂之间的AUC和Css显著降低，而A组未出现此情况。A组第1剂后的Cl/F值显著高于B组，但第13剂后并非如此。未观察到因白消安剂量增加导致的毒性增加。我们得出结论，与16mg/kg相比，600mg/m²的白消安导致药物的全身暴露量高得多，且重型β地中海贫血儿童的毒性未增加。
