利巴韦林对人类免疫缺陷病毒-丙型肝炎病毒合并感染患者体内核苷类逆转录酶抑制剂细胞内及血浆药代动力学的影响：一项随机临床研究结果
Effect of ribavirin on intracellular and plasma pharmacokinetics of nucleoside reverse transcriptase inhibitors in patients with human immunodeficiency virus-hepatitis C virus coinfection: results of a randomized clinical study.
作者信息
Rodriguez-Torres M, Torriani F J, Soriano V, Borucki M J, Lissen E, Sulkowski M, Dieterich D, Wang K, Gries J-M, Hoggard P G, Back D
机构信息
Fundacion de Investigación de Diego, Santurce, Puerto Rico.
出版信息
Antimicrob Agents Chemother. 2005 Oct;49(10):3997-4008. doi: 10.1128/AAC.49.10.3997-4008.2005.
The intracellular triphosphorylation and plasma pharmacokinetics of lamivudine (3TC), stavudine (d4T), and zidovudine (ZDV) were assessed in a pharmacokinetic substudy, in 56 human immunodeficiency virus-hepatitis C virus (HIV-HCV) coinfected patients receiving peginterferon alfa-2a (40KD) 180 microg/week plus either placebo or ribavirin (RBV) 800 mg/day in the AIDS PEGASYS Ribavirin International Coinfection Trial. There were no significant differences between patients treated with RBV and placebo in plasma pharmacokinetics parameters for the nucleoside reverse transcriptase inhibitors (NRTIs) at steady state (weeks 8 to 12): ratios of least squares mean of area under the plasma concentration-time curve (AUC(0-12 h)) were 1.17 (95% confidence interval, 0.91 to 1.51) for 3TC, 1.44 (95% confidence interval, 0.58 to 3.60) for d4T and 0.85 (95% confidence interval, 0.50 to 1.45) for ZDV, and ratios of least squares mean plasma C(max) were 1.33 (95% confidence interval, 0.99 to 1.78), 1.06 (95% confidence interval, 0.68 to 1.65), and 0.84 (95% confidence interval, 0.46 to 1.53), respectively. Concentrations of NRTI triphosphate (TP) metabolites in relation to those of the triphosphates of endogenous deoxythymidine-triphosphate (dTTP) and deoxcytidine-triphosphate (dCTP) were similar in the RBV and placebo groups. Differences (RBV to placebo) in least squares mean ratios of AUC(0-12 h) at steady state were 0.274 (95% confidence interval, -0.37 to 0.91) for 3TC-TP:dCTP, 0.009 (95% confidence interval, -0.06 to 0.08) for d4T-TP:dTTP, and -0.081 (95% confidence interval, -0.40 to 0.24) for ZDV-TP:dTTP. RBV did not adversely affect HIV-1 replication. In summary, RBV 800 mg/day administered in combination with peginterferon alfa-2a (40KD) does not significantly affect the intracellular phosphorylation or plasma pharmacokinetics of 3TC, d4T, and ZDV in HIV-HCV-coinfected patients.
在一项药代动力学子研究中，对56例合并感染人类免疫缺陷病毒和丙型肝炎病毒（HIV-HCV）的患者进行了拉米夫定（3TC）、司他夫定（d4T）和齐多夫定（ZDV）的细胞内三磷酸化及血浆药代动力学评估。这些患者在艾滋病聚乙二醇化干扰素α-2a（40KD）国际合并感染试验中，接受每周180μg聚乙二醇化干扰素α-2a（40KD）加安慰剂或每日800mg利巴韦林（RBV）治疗。在稳态时（第8至12周），接受RBV治疗的患者与接受安慰剂治疗的患者相比，核苷类逆转录酶抑制剂（NRTIs）的血浆药代动力学参数无显著差异：3TC的血浆浓度-时间曲线下面积（AUC(0-12 h)）的最小二乘均值之比为1.17（95%置信区间，0.91至1.51），d4T为1.44（95%置信区间，0.58至3.60），ZDV为0.85（95%置信区间，0.50至1.45）；血浆C(max)的最小二乘均值之比分别为1.33（95%置信区间，0.99至1.78）、1.06（95%置信区间，0.68至1.65）和0.84（95%置信区间，0.46至1.53）。RBV组和安慰剂组中，NRTI三磷酸（TP）代谢物与内源性脱氧胸苷三磷酸（dTTP）和脱氧胞苷三磷酸（dCTP）三磷酸的浓度相似。稳态时AUC(0-12 h)最小二乘均值之比的差异（RBV与安慰剂相比），3TC-TP:dCTP为0.274（95%置信区间，-0.37至0.91），d4T-TP:dTTP为0.009（95%置信区间，-0.06至0.08），ZDV-TP:dTTP为-0.081（95%置信区间，-0.40至0.24）。RBV对HIV-1复制无不良影响。总之，在HIV-HCV合并感染患者中，每日800mg RBV与聚乙二醇化干扰素α-2a（40KD）联合使用，对3TC、d4T和ZDV的细胞内磷酸化或血浆药代动力学无显著影响。
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