Cooney G F, Dunn S P, Sommerauer J, Lindsay C, McDiarmid S, Choc M G, Smith H T, Chang C T, Wong R L
Department of Surgery, St Christopher's Hospital for Children, Temple University School of Pharmacy, Philadelphia, PA, USA.
Liver Transpl Surg. 1999 Mar;5(2):112-8. doi: 10.1002/lt.500050206.
Black transplant recipients are associated with low cyclosporine bioavailability, which may contribute to the poorer clinical outcomes observed with these patients. In this analysis, we compared cyclosporine exposure in black (n = 9) and nonblack (n = 18) pediatric maintenance liver transplant recipients by using steady-state pharmacokinetic profiles obtained after administration of the original and microemulsion formulations of cyclosporine. Treatment with the original cyclosporine formulation resulted in lower mean dose-normalized, area under the concentration-versus-time curve values for black compared with nonblack pediatric liver transplant recipients. On conversion to the microemulsion formulation of cyclosporine, black and nonblack patients experienced increases in cyclosporine bioavailability of 102% and 39%, respectively (P =.009 and P =.001). Because the increase in mean bioavailability was substantially greater for blacks, area under the concentration-versus-time curve values for this pediatric subpopulation became similar to those levels obtained for nonblacks receiving the microemulsion formulation for cyclosporine. When patients were further stratified by age, ethnic differences in bioavailability with the original formulation of cyclosporine were most apparent in the 1- to 5-year age group. Conversion to the microemulsion formulation resulted in a 164% increase (P =.05) in bioavailability for black patients within this age group such that, again, these levels became similar to area under the concentration-versus-time curve values obtained for young nonblacks receiving cyclosporine for microemulsion. Improvements in cyclosporine bioavailability after administration of the microemulsion formulation of cyclosporine may translate to improved long-term graft and patient outcomes for black pediatric liver transplant recipients.
黑人肝移植受者的环孢素生物利用度较低，这可能是导致这些患者临床预后较差的原因之一。在本分析中，我们通过使用环孢素原研制剂和微乳剂给药后获得的稳态药代动力学曲线，比较了黑人（n = 9）和非黑人（n = 18）儿科维持性肝移植受者的环孢素暴露情况。与非黑人儿科肝移植受者相比，使用环孢素原研制剂治疗后，黑人患者的平均剂量标准化浓度-时间曲线下面积值较低。转换为环孢素微乳剂后，黑人和非黑人患者的环孢素生物利用度分别提高了102%和39%（P = 0.009和P = 0.001）。由于黑人患者平均生物利用度的增加幅度明显更大，该儿科亚组的浓度-时间曲线下面积值变得与接受环孢素微乳剂的非黑人患者相似。当按年龄进一步分层时，环孢素原研制剂在1至5岁年龄组中生物利用度的种族差异最为明显。转换为微乳剂后，该年龄组黑人患者的生物利用度提高了164%（P = 0.05），使得这些水平再次与接受环孢素微乳剂的年轻非黑人患者的浓度-时间曲线下面积值相似。环孢素微乳剂给药后环孢素生物利用度的改善可能转化为黑人儿科肝移植受者长期移植物和患者预后的改善。
