Nasser Azmi F, Heidbreder Christian, Liu Yongzhen, Fudala Paul J
Reckitt Benckiser Pharmaceuticals Inc., Richmond, VA, 23235, USA,
Clin Pharmacokinet. 2015 Aug;54(8):837-49. doi: 10.1007/s40262-015-0238-6.
Suboxone(®) is a sublingual tablet of buprenorphine/naloxone, approved for the treatment of opioid dependence. The objective of this study was to quantify the impact of hepatic impairment or hepatitis C virus infection on the pharmacokinetics of buprenorphine or naloxone and their major metabolites.
Forty-three subjects received a single dose of a Suboxone 2.0/0.5-mg tablet. Blood samples were collected up to 168 h and pharmacokinetic parameters were calculated using non-compartmental analysis. Statistical analysis was performed using analysis of covariance.
Pharmacokinetic parameters were derived from 33 subjects. Compared with healthy subjects, for patients with severe hepatic impairment, total and peak exposures increased to 281.4 % [90 % confidence interval 187.1-423.3] and 171.8 % [117.9-250.2] for buprenorphine, 1401.9 % [707.6-2777.5] and 1129.8 % [577.2-2211.4] for naloxone. For moderate hepatic impaired subjects, naloxone total and peak exposure increased to 317.6 % [164.9-611.5] and 270.0 % [141.9-513.9]. For buprenorphine, only total exposure increased to 163.9 % [110.8-242.3]. Changes in maximum observed plasma concentration, area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration, and area under the plasma concentration-time curve from time zero to infinity of buprenorphine or naloxone in subjects with mild hepatic impairment or with hepatitis C virus infection were within twofold of those of healthy subjects. Serious adverse events were not observed.
Severe and moderate hepatic impairment significantly increased exposure of naloxone and to a lesser extent of buprenorphine. Therefore, buprenorphine/naloxone combination products should generally be avoided in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. However, buprenorphine/naloxone products may be used with caution for maintenance treatment in patients with moderate hepatic impairment who have initiated treatment on a buprenorphine product without naloxone [Registered at ClinicalTrials.gov as NCT01846455].
舒倍生（Suboxone®）是一种含丁丙诺啡/纳洛酮的舌下片，已获批用于治疗阿片类药物依赖。本研究的目的是量化肝功能损害或丙型肝炎病毒感染对丁丙诺啡或纳洛酮及其主要代谢产物药代动力学的影响。
43名受试者单次服用一片2.0/0.5mg的舒倍生片。采集血样长达168小时，并使用非房室分析计算药代动力学参数。采用协方差分析进行统计分析。
药代动力学参数来自33名受试者。与健康受试者相比，对于重度肝功能损害患者，丁丙诺啡的总暴露量和峰暴露量分别增加至281.4%[90%置信区间187.1 - 423.3]和171.8%[117.9 - 250.2]，纳洛酮分别增加至1401.9%[707.6 - 2777.5]和1129.8%[577.2 - 2211.4]。对于中度肝功能损害受试者，纳洛酮的总暴露量和峰暴露量分别增加至317.6%[164.9 - 611.5]和270.0%[141.9 - 513.9]。对于丁丙诺啡，仅总暴露量增加至163.9%[110.8 - 242.3]。轻度肝功能损害或丙型肝炎病毒感染受试者中丁丙诺啡或纳洛酮的最大观察血浆浓度、从时间零点至最后可定量浓度的血浆浓度 - 时间曲线下面积以及从时间零点至无穷大的血浆浓度 - 时间曲线下面积的变化在健康受试者的两倍以内。未观察到严重不良事件。
重度和中度肝功能损害显著增加纳洛酮的暴露量，对丁丙诺啡的暴露量影响较小。因此，重度肝功能损害患者通常应避免使用丁丙诺啡/纳洛酮复方制剂，中度肝功能损害患者可能也不适用。然而，对于已开始使用不含纳洛酮的丁丙诺啡产品进行治疗的中度肝功能损害患者，在维持治疗时可谨慎使用丁丙诺啡/纳洛酮产品[在ClinicalTrials.gov注册为NCT01846455]。
