Smith Don E, Jeganathan Sarangapany, Ray John
Albion Street Centre, Sydney, NSW, Australia.
HIV Clin Trials. 2006 Jan-Feb;7(1):34-8. doi: 10.1310/0KX0-H9VH-99EE-5D0L.
Atazanavir (ATV) is recommended to be dosed at 400 mg once daily or 300 mg daily coadministered with 100 mg ritonavir (RTV).
31 male patients receiving ATV either alone or boosted with RTV for more than 2 weeks had ATV concentration measured by high performance liquid chromatography (HPLC). ATV concentrations were adjusted to obtain a 24-hour trough level using a standard pharmacokinetic formula.
25 samples were taken from patients who received 300 mg ATV, 6 with 200 mg, 3 with 400 mg, and 2 with 150 mg, all boosted with 100 mg RTV. In the unboosted group, patients received 400 mg (7) or 600 mg (2). The median adjusted 24-hour trough ATV concentration was 630 ng/mL (interquartile range [IQR] 355-1034) in the boosted and 113 ng/mL (IQR 50-225) in the unboosted group (p = .001). Median serum bilirubin concentration was 34 IU/L (IQR 27.5-49) and 41 IU/L (IQR 31-45) in the boosted and unboosted groups, respectively. In the boosted group, high ATV concentrations were significantly correlated with increased serum bilirubin concentrations (p = .003).
ATV concentrations showed considerable interpatient variability. Bilirubin concentrations are an indicator of high ATV concentrations and may prove to be useful in selecting patients for therapeutic drug monitoring (TDM).
阿扎那韦（ATV）推荐剂量为每日400毫克，或每日300毫克与100毫克利托那韦（RTV）联合使用。
31名接受ATV单药治疗或联合RTV增强治疗超过2周的男性患者，通过高效液相色谱法（HPLC）测量ATV浓度。使用标准药代动力学公式调整ATV浓度以获得24小时谷浓度。
从接受300毫克ATV的患者中采集了25份样本，6名接受200毫克，3名接受400毫克，2名接受150毫克，均联合100毫克RTV增强治疗。在未增强治疗组中，患者接受400毫克（7例）或600毫克（2例）。增强治疗组调整后的ATV 24小时谷浓度中位数为630纳克/毫升（四分位间距[IQR] 355 - 1034），未增强治疗组为113纳克/毫升（IQR 50 - 225）（p = .001）。增强治疗组和未增强治疗组的血清胆红素浓度中位数分别为34国际单位/升（IQR 27.5 - 49）和41国际单位/升（IQR 31 - 45）。在增强治疗组中，高ATV浓度与血清胆红素浓度升高显著相关（p = .003）。
ATV浓度在患者间显示出相当大的变异性。胆红素浓度是高ATV浓度的一个指标，可能在选择患者进行治疗药物监测（TDM）方面有用。
