Ribera Esteban, Azuaje Carlos, Lopez Rosa M, Domingo Pere, Curran Adria, Feijoo Maria, Pou Leonor, Sánchez Paquita, Sambeat Maria Antonia, Colomer Joan, Lopez-Colomes Josep Lluis, Crespo Manuel, Falcó Vicenç, Ocaña Imma, Pahissa Albert
Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
J Antimicrob Chemother. 2007 Apr;59(4):690-7. doi: 10.1093/jac/dkl552. Epub 2007 Feb 16.
To assess plasma steady-state pharmacokinetics (PK) of rifampicin, isoniazid, saquinavir and ritonavir in HIV and tuberculosis (TB) co-infected patients, and investigate potential interactions between TB drugs and protease inhibitors (PIs).
Open-label, single-arm, sequential PK study including 22 patients with HIV infection and TB. During the first 2 months, patients received rifampicin, isoniazid and pyrazinamide, with or without ethambutol (first PK study, n = 22). Then patients stopped pyrazinamide and ethambutol and started once-daily antiretroviral therapy (ART) with didanosine, lamivudine, ritonavir (200 mg) and saquinavir (1600 mg) (second PK study, n = 18). Patients stopped all TB drugs after 9 months continuing the same ART (third PK study, n = 15). Differences between TB drug parameters in the first and second PK studies, and between PI parameters in the second and third PK studies were used to assess interactions.
Rifampicin and isoniazid pharmacokinetics did not change substantially with saquinavir and ritonavir. A significant 39.5%, 34.9% and 48.7% reduction in median saquinavir AUC(0-24), C(max) and C(trough), respectively, was seen with rifampicin and isoniazid. Ritonavir AUC(0-24), C(max) and C(trough) decreased 42.5%, 49.6% and 64.3%, respectively, with rifampicin and isoniazid.
There was a significant interaction between saquinavir, ritonavir and rifampicin, with reduction in median plasma concentrations of saquinavir and ritonavir. Saquinavir should be given with caution in patients receiving rifampicin. Twice-daily dosing or higher saquinavir doses in once-daily administration should be tested to obtain more appropriate plasma levels.
评估利福平、异烟肼、沙奎那韦和利托那韦在人类免疫缺陷病毒（HIV）合并结核病（TB）患者中的血浆稳态药代动力学（PK），并研究抗结核药物与蛋白酶抑制剂（PIs）之间的潜在相互作用。
开放标签、单臂、序贯PK研究，纳入22例HIV感染合并TB患者。在最初2个月内，患者接受利福平、异烟肼和吡嗪酰胺，可加用或不加用乙胺丁醇（首次PK研究，n = 22）。然后患者停用吡嗪酰胺和乙胺丁醇，开始每日一次的抗逆转录病毒治疗（ART），使用去羟肌苷、拉米夫定、利托那韦（200mg）和沙奎那韦（1600mg）（第二次PK研究，n = 18）。9个月后患者停用所有抗结核药物，继续相同的ART治疗（第三次PK研究，n = 15）。通过比较首次和第二次PK研究中抗结核药物参数的差异，以及第二次和第三次PK研究中PI参数的差异来评估相互作用。
利福平与异烟肼的药代动力学在联合使用沙奎那韦和利托那韦时无显著变化。利福平与异烟肼联合使用时，沙奎那韦的中位AUC(0 - 24)、C(max)和C(trough)分别显著降低39.5%、34.9%和48.7%。利福平与异烟肼联合使用时，利托那韦的AUC(0 - 24)、C(max)和C(trough)分别降低42.5%、49.6%和64.3%。
沙奎那韦、利托那韦与利福平之间存在显著相互作用，导致沙奎那韦和利托那韦的血浆中位浓度降低。接受利福平治疗的患者应谨慎使用沙奎那韦。应测试每日两次给药或每日一次给药时更高剂量的沙奎那韦，以获得更合适的血浆水平。
