Balk Jiska M, Haenen Guido Rmm, Koc Özgür M, Peters Ron, Bast Aalt, van der Vijgh Wim Jf, Koek Ger H
Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
Pharmgenomics Pers Med. 2015 Aug 12;8:137-44. doi: 10.2147/PGPM.S82782. eCollection 2015.
The combination of ribavirin (RBV) and pegylated interferon (PEG-IFN) is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens.
In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry.
Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose) was significantly different between the two groups (P>0.05). Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0.05). No significant differences in the hematological profile were observed (P>0.05).
The standard twice-daily RBV regimen is interchangeable with the once-daily regimen. The once-daily regimen will improve compliance and opens the opportunity to combine RBV with other drugs dosed once a day, in a single pill.
利巴韦林（RBV）与聚乙二醇干扰素（PEG-IFN）联合用药对慢性丙型肝炎感染有效。将RBV的服药频率从每日两次减至每日一次可提高依从性，并为将RBV与新型、更具特异性的直接作用抗病毒药物制成复方单片制剂创造机会。因此，本研究旨在评估RBV每日一次与每日两次给药方案的药代动力学特征。次要目的是确定两种治疗方案的耐受性以及副作用的严重程度和差异。
在这项随机开放标签交叉研究中，12例体重超过75kg的慢性1型丙型肝炎感染患者接受每周180μg PEG-IFN和每日1200mg RBV治疗，疗程24周。患者先接受每日1200mg RBV，共12周，随后接受每日两次、每次600mg RBV，共12周，或反之。除药代动力学特征外，还记录血液学指标和副作用。采用液相色谱-串联质谱法测定血浆中RBV浓度。
12例患者中有8例完成了研究。两组间RBV达到血浆峰浓度的时间以及AUC0-last（根据剂量差异校正）均无显著差异（P>0.05）。此外，每日一次给药方案的副作用并不比每日两次给药方案多（P>0.05）。血液学指标未见显著差异（P>0.05）。
标准的RBV每日两次给药方案与每日一次给药方案可互换。每日一次给药方案可提高依从性，并为将RBV与其他每日一次给药的药物制成复方单片制剂创造机会。
