National Tuberculosis Program, Ministry of Health, Ouagadougou, Burkina Faso.
J Antimicrob Chemother. 2012 Feb;67(2):469-72. doi: 10.1093/jac/dkr445. Epub 2011 Oct 25.
Low plasma concentrations of rifampicin, an essential antituberculosis drug, have been reported particularly among HIV co-infected persons. In a prospective, longitudinal study we measured rifampicin systemic exposure at different timepoints during highly active antiretroviral therapy (HAART).
From May 2006 to April 2007, 16 tuberculosis (TB)/HIV co-infected patients were enrolled in Ouagadougou, Burkina Faso. All patients received fixed dose combinations of rifampicin, isoniazid, pyrazinamide and ethambutol under direct observation and HAART, consisting of a fixed dose combination of stavudine, lamivudine and nevirapine. Rifampicin concentrations during the dosing interval were determined by HPLC at three different timepoints: (i) after 2 weeks of TB therapy and before starting HIV therapy (T0); (ii) after 4 weeks of combined therapy (T1); and (iii) after 10 weeks of combined therapy (T2).
The median values of the area under the curve (AUC(0-24)) of rifampicin increased by 39% at T1 (15.69 μg · h/mL; P = 0.01) and by 83% at T2 (20.65 μg · h/mL; P = 0.001) compared with T0 (11.28 μg · h/mL). Similar variations were observed for the median C(max) at T0 (2.24 μg/mL) compared with T2 (2.83 μg/mL; P = 0.003). However, none of the subjects had C(max) levels >8 μg/mL at either T0 or T2.
Rifampicin systemic exposure increased during combined TB and HIV therapy, possibly due to increased drug absorption or decreased oral clearance, but remained invariably low in this population. Studies to define the C(max) rifampicin concentrations, which are associated with a significantly increased risk of treatment failure, are urgently warranted.
利福平是一种重要的抗结核药物，有报道称其在 HIV 合并感染者中的血药浓度较低。在一项前瞻性、纵向研究中，我们在高效抗逆转录病毒治疗（HAART）的不同时间点测量了利福平的全身暴露情况。
2006 年 5 月至 2007 年 4 月，在布基纳法索瓦加杜古招募了 16 例结核（TB）/HIV 合并感染者。所有患者均接受了利福平、异烟肼、吡嗪酰胺和乙胺丁醇的固定剂量联合治疗，并在直接观察下接受了包含司他夫定、拉米夫定和奈韦拉平的固定剂量联合 HAART。在三个不同时间点通过 HPLC 测定利福平的血药浓度：（i）在开始抗结核治疗和 HIV 治疗前的第 2 周（T0）；（ii）联合治疗后的第 4 周（T1）；和（iii）联合治疗后的第 10 周（T2）。
与 T0（11.28μg·h/mL）相比，T1（15.69μg·h/mL；P=0.01）和 T2（20.65μg·h/mL；P=0.001）时利福平的 AUC（0-24）中位数增加了 39%。T0 时的 C(max)中位数（2.24μg/mL）与 T2 时（2.83μg/mL；P=0.003）相比也有类似的变化。然而，在 T0 或 T2 时，均无受试者的 C(max)水平>8μg/mL。
在联合抗结核和 HIV 治疗期间，利福平的全身暴露增加，可能是由于药物吸收增加或口服清除率降低，但在该人群中仍然不变。迫切需要研究确定 C(max)利福平浓度，因为这与治疗失败的风险显著增加有关。
