Justesen Ulrik S, Klitgaard Niels A, Brosen Kim, Pedersen Court
Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark.
Br J Clin Pharmacol. 2003 Jan;55(1):100-6. doi: 10.1046/j.1365-2125.2003.01734.x.
To evaluate the safety and the pharmacokinetic interaction between amprenavir and delavirdine after multiple dose administration in healthy volunteers.
This was a prospective, open-label, randomized, controlled, two-sequence, two-period multiple dose study with 18 healthy subjects. Volunteers were randomly assigned to amprenavir, 600 mg twice a day, or delavirdine, 600 mg twice a day, for 10 days, followed by both drugs for another 10 days with pharmacokinetic evaluation on day 10 and day 20. Adverse events were recorded throughout the study.
Amprenavir decreased all the delavirdine pharmacokinetic parameters apart from tmax. Delavirdine C12h dropped from 7,916 to 933 ng ml-1 (median decrease 5,930 ng ml-1, 95% CI 3,013, 8,955 ng ml-1). A decrease in amprenavir t(1/2) was also seen leading to almost identical median amprenavir C24h values. No serious clinical adverse events were observed during the study. The most frequently reported effects were gastrointestinal symptoms, headache, fatigue and rash.
Amprenavir is an effective inducer of delavirdine metabolism, probably through its effect on hepatic CYP3A4. This could have consequences in other drug-drug interaction situations. Delavirdine is an inhibitor of amprenavir metabolism. The regimen of amprenavir 600 mg and delavirdine 600 mg twice a day is not recommended when an antiretroviral effect from delavirdine is required.
评估健康志愿者多次给药后安普那韦与地拉韦啶之间的安全性及药代动力学相互作用。
这是一项前瞻性、开放标签、随机、对照、双序列、双周期的多剂量研究，共有18名健康受试者。志愿者被随机分配接受安普那韦（每日两次，每次600毫克）或地拉韦啶（每日两次，每次600毫克），持续10天，随后两种药物联合使用10天，并在第10天和第20天进行药代动力学评估。在整个研究过程中记录不良事件。
除tmax外，安普那韦降低了地拉韦啶所有的药代动力学参数。地拉韦啶C12h从7916降至933纳克/毫升（中位数下降5930纳克/毫升，95%置信区间3013, 8955纳克/毫升）。安普那韦的t(1/2)也有所下降，导致安普那韦C24h的中位数几乎相同。研究期间未观察到严重的临床不良事件。最常报告的效应是胃肠道症状、头痛、疲劳和皮疹。
安普那韦可能通过对肝脏CYP3A4的作用，是地拉韦啶代谢的有效诱导剂。这可能在其他药物相互作用情况下产生影响。地拉韦啶是安普那韦代谢的抑制剂。当需要地拉韦啶的抗逆转录病毒效应时，不推荐每日两次，每次600毫克安普那韦与600毫克地拉韦啶的治疗方案。
