Jacqz-Aigrain E, Macher M A, Sauvageon-Marthe H, Brun P, Loirat C
Department of Clinical Pharmacology, Hôpital Robert-Debré, Pairs, France.
Pediatr Nephrol. 1992 Mar;6(2):194-6. doi: 10.1007/BF00866315.
Three cytomegalovirus (CMV)-seronegative children received renal transplants from CMV-seropositive donors and developed clinical symptoms of CMV infection between days 20 and 34 post transplantation. Ganciclovir (DHPG) was administered in a 1-h infusion, and the doses and dose intervals were adapted to the degree of renal insufficiency, according to the manufacturer's recommendations for adults. Individual pharmacokinetic parameters of DHPG were determined and were markedly altered. Plasma clearances were 0.4, 1.1 and 2.2 ml/min per kg and were related to individual creatinine clearances (20, 45 and 60 ml/min per 1.73 m2); the corresponding elimination half-lives were 23.7, 9.9 and 3.9 h. In two patients, the doses had to be further reduced in order to maintain plasma levels within the recommended values for peak and trough plasma concentrations. Therefore, monitoring of DHPG appears essential in adjusting dosage for optimal efficacy and minimal toxicity.
三名巨细胞病毒（CMV）血清学阴性的儿童接受了来自CMV血清学阳性供体的肾移植，并在移植后第20至34天出现了CMV感染的临床症状。更昔洛韦（DHPG）采用1小时静脉输注给药，剂量和给药间隔根据肾功能不全程度进行调整，遵循制造商针对成人的建议。测定了DHPG的个体药代动力学参数，发现其有显著改变。血浆清除率分别为每千克体重0.4、1.1和2.2毫升/分钟，与个体肌酐清除率（每1.73平方米体表面积20、45和60毫升/分钟）相关；相应的消除半衰期分别为23.7、9.9和3.9小时。在两名患者中，为了将血浆水平维持在推荐的峰浓度和谷浓度范围内，必须进一步降低剂量。因此，监测DHPG对于调整剂量以实现最佳疗效和最小毒性似乎至关重要。
