McCance-Katz Elinore F, Rainey Petrie M, Friedland Gerald, Jatlow Peter
Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
Clin Infect Dis. 2003 Aug 15;37(4):476-82. doi: 10.1086/376907. Epub 2003 Aug 1.
This study examines the pharmacokinetic/pharmacodynamic interactions between (1) lopinavir-ritonavir (L/R), a fixed combination of protease inhibitors used for the treatment of HIV disease, and (2) ritonavir alone at the same dosage as that in the L/R formulation, with methadone, an opiate frequently used in substance abuse pharmacotherapy for opioid (heroin)-dependent injection drug users, many of whom are infected with HIV. L/R was associated with significant reductions in the methadone area under the concentration-time curve (P<.001), maximum concentration (P<.001), and minimum concentration (P<.001), as well as increased methadone oral clearance (P<.001) and increased opiate withdrawal symptoms (P=.013), whereas ritonavir use alone modestly and nonsignificantly increased methadone concentrations. Lopinavir is a potent inducer of methadone metabolism, and treatment with L/R requires clinical monitoring and increased methadone doses in some patients, whereas ritonavir has no significant effect on methadone metabolism.
本研究考察了用于治疗HIV疾病的蛋白酶抑制剂固定复方洛匹那韦-利托那韦（L/R）与单独使用的相同剂量（等同于L/R制剂中的剂量）的利托那韦，分别与美沙酮之间的药代动力学/药效学相互作用。美沙酮是常用于阿片类（海洛因）依赖注射吸毒者药物滥用药物治疗的一种阿片类药物，其中许多人感染了HIV。L/R与美沙酮浓度-时间曲线下面积显著降低（P<0.001）、最大浓度显著降低（P<0.001）、最低浓度显著降低（P<0.001）相关，同时美沙酮口服清除率增加（P<0.001）以及阿片类戒断症状增加（P=0.013），而单独使用利托那韦使美沙酮浓度适度增加但无显著意义。洛匹那韦是美沙酮代谢的强效诱导剂，使用L/R治疗时需要进行临床监测，且部分患者需增加美沙酮剂量，而利托那韦对美沙酮代谢无显著影响。
