Peck R W, Crome P, Wood M J, McKendrick M W, Bannister B, Mandal B K, Crooks R J
Wellcome Research Laboratories, Beckenham, Kent, UK.
J Antimicrob Chemother. 1996 Mar;37(3):583-97. doi: 10.1093/jac/37.3.583.
Netivudine is a nucleoside analogue with potent anti-varicella zoster virus activity. We now report two open studies of the pharmacokinetics and tolerability of netivudine in doses of 50, 100 and 200 mg twice daily. In one study, healthy volunteers received an initial, single dose followed, a week later, by repeat dosing for 9 1/2 days; in the other, patients with shingles were treated for 8 days and data were also recorded for rash resolution and pain duration and intensity. Netivudine was well tolerated in both studies. Plasma concentrations were similar in patients and healthy volunteers and increased in proportion to dose. Steady state concentrations were 15-25% lower than expected from single dose data, probably because of slightly decreased netivudine absorption after food. Elimination half-life was l4-20 h. Plasma concentrations of 5-propynyluracil (5-PU), the main metabolite of netivudine, did not increase in proportion to the netivudine dose and tended to be higher in patients than volunteers. 5-PU concentrations remained elevated for up to 72 h after the last netivudine dose, suggesting continued but slow release from unabsorbed netivudine in the gut lumen. New lesion formation ceased and vesicles crusted most quickly in the 200 mg group; zoster-associated pain intensity, was reduced in a dose-related manner.
奈替夫定是一种具有强效抗水痘带状疱疹病毒活性的核苷类似物。我们现在报告两项关于奈替夫定每日两次服用50、100和200毫克剂量的药代动力学和耐受性的开放性研究。在一项研究中，健康志愿者先接受一次初始单剂量给药，一周后重复给药9.5天；在另一项研究中，带状疱疹患者接受8天治疗，并记录皮疹消退情况、疼痛持续时间和强度的数据。在两项研究中，奈替夫定都具有良好的耐受性。患者和健康志愿者的血浆浓度相似，且与剂量成比例增加。稳态浓度比单剂量数据预期的低15%-25%，这可能是因为进食后奈替夫定的吸收略有下降。消除半衰期为14-20小时。奈替夫定的主要代谢产物5-丙炔基尿嘧啶（5-PU）的血浆浓度与奈替夫定剂量不成比例增加，且在患者中往往高于志愿者。在最后一次服用奈替夫定后，5-PU浓度在长达72小时内一直升高，这表明肠道腔内未吸收的奈替夫定持续但缓慢释放。在200毫克组中，新皮损形成停止，水疱结痂最快；带状疱疹相关疼痛强度呈剂量相关降低。
