Bruzzese V L, Gillum J G, Israel D S, Johnson G L, Kaplowitz L G, Polk R E
School of Medicine, Virginia Commonwealth University/Medical College of Virginia, Richmond, VA 23298-0533, USA.
Antimicrob Agents Chemother. 1995 May;39(5):1050-3. doi: 10.1128/AAC.39.5.1050.
Fluconazole inhibits cytochrome P-450-mediated enzymatic metabolism of several drugs. Since hepatic metabolism is partially responsible for 2',3'-dideoxyinosine (didanosine or ddI) elimination, fluconazole therapy may lead to increased ddI concentrations in serum and subsequent concentration-dependent adverse effects. The purpose of this study was to determine if ddI pharmacokinetics are influenced by a 7-day course of oral fluconazole. Twelve adults with human immunodeficiency virus (HIV) who had received a constant dosage of ddI for at least 2 weeks were investigated. On study day 1, multiple serum samples for determination of ddI concentrations were obtained over 12 h. Then subjects received a 7-day course of oral fluconazole (200 mg every 12 h for two doses and then 200 mg once daily for 6 days) while ddI therapy continued. Following the last dose of fluconazole, serum samples for determination of ddI concentrations were again obtained over 12 h. ddI concentrations in serum were analyzed by radioimmunoassay. In contrast to previously published data, there was marked between-subject variability in ddI areas under the concentration-time curve, even when the dose was normalized for weight. No significant differences were found between mean ddI areas under the concentration-time curve from 0 to 12 h on study day 1 (1,528 +/- 902 ngx.hr/ml) and following fluconazole treatment (1,486 +/- 649 ngx.hr/ml) . There were no significant differences in other pharmacokinetic parameters, such as ddI peak concentrations in serum (971 +/- 509 and 942 +/- 442 ng/ml) or half-lives (80 +/- 32 and 85 +/- 21 min.) before and after fluconazole treatment, respectively. We conclude that a 7-day course of oral fluconazole does not significantly alter ddI pharmacokinetics in adults that are infected with human immunodeficiency virus.
氟康唑可抑制细胞色素P - 450介导的多种药物的酶促代谢。由于肝脏代谢部分参与2',3'-双脱氧肌苷（去羟肌苷或ddI）的消除过程，氟康唑治疗可能会导致血清中ddI浓度升高以及随后的浓度依赖性不良反应。本研究的目的是确定口服氟康唑7天疗程是否会影响ddI的药代动力学。对12名接受至少2周恒定剂量ddI治疗的成人人类免疫缺陷病毒（HIV）感染者进行了研究。在研究的第1天，在12小时内采集多个血清样本以测定ddI浓度。然后受试者在继续接受ddI治疗的同时接受为期7天的口服氟康唑疗程（每12小时200mg，共2剂，然后每天1次200mg，共6天）。在最后一剂氟康唑之后，再次在12小时内采集血清样本以测定ddI浓度。血清中的ddI浓度通过放射免疫测定法进行分析。与先前发表的数据相反，即使根据体重对剂量进行了标准化，ddI浓度 - 时间曲线下面积在受试者之间仍存在显著差异。在研究的第1天（1,528±902 ngx.hr/ml）和氟康唑治疗后（1,486±649 ngx.hr/ml），0至12小时的ddI浓度 - 时间曲线下平均面积之间未发现显著差异。氟康唑治疗前后的其他药代动力学参数，如血清中ddI的峰值浓度（分别为971±509和942±442 ng/ml）或半衰期（分别为80±32和85±21分钟）也没有显著差异。我们得出结论，口服氟康唑7天疗程不会显著改变感染人类免疫缺陷病毒的成人的ddI药代动力学。
