Fowles S E, Pratt S K, Laroche J, Prince W T
Drug Metabolism and Pharmacokinetics Department, SmithKline Beecham Pharmaceuticals, Welwyn, Hertfordshire, UK.
Eur J Clin Pharmacol. 1994;46(4):355-9. doi: 10.1007/BF00194405.
Famciclovir has been shown to have potent and selective activity against herpesviruses. The possibility of a pharmacokinetic interaction between the anti-viral agent, famciclovir and allopurinol has been investigated in twelve healthy male volunteers following a single oral dose of famciclovir (500 mg) in the presence and absence of steady-state levels of allopurinol (300 mg). Similarly, the pharmacokinetic profiles of allopurinol and oxypurinol prior to and following a single dose of famciclovir were compared. Mean values of Cmax, AUC and terminal-phase half-life for penciclovir following administration of famciclovir alone at 3.3 micrograms.ml-1, 8.8 micrograms.h.ml-1 and 2.1 h, respectively were unchanged by co-administration of allopurinol. Similarly, mean urinary recovery and renal clearance values of penciclovir following famciclovir alone were 56.8% and 27 l.h-1, and when given with allopurinol 59.7% and 27.5 l.h-1, respectively. No evidence of accumulation of the inactive precursor to penciclovir, BRL 42359, was noted as a result of co-administration of the two drugs. Mean steady-state Cmax, AUC and terminal-phase half-life values for allopurinol after co-administration of allopurinol with famciclovir also appeared unchanged from values obtained after dosing of allopurinol alone, at 2.12 micrograms.ml-1, 5.73 micrograms.h.ml-1 and 1.38 h, respectively. Mean Cmax and AUC values of the active metabolite of allopurinol, oxypurinol were 11.2 micrograms.ml-1 and 96.0 micrograms.h.ml-1, respectively, and these were also unaltered by co-administration of famciclovir with allopurinol, with values of 10.6 micrograms/ml and 89.8 micrograms.h/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
泛昔洛韦已显示出对疱疹病毒具有强大的选择性活性。在12名健康男性志愿者中,研究了抗病毒药物泛昔洛韦与别嘌醇之间药代动力学相互作用的可能性,这些志愿者在有和没有稳态水平别嘌醇(300毫克)的情况下单次口服泛昔洛韦(500毫克)。同样,比较了单次服用泛昔洛韦前后别嘌醇和氧嘌呤醇的药代动力学特征。单独服用泛昔洛韦后喷昔洛韦的Cmax、AUC和终末相半衰期的平均值分别为3.3微克·毫升-1、8.8微克·小时·毫升-1和2.1小时,与别嘌醇合用后这些值未发生变化。同样,单独服用泛昔洛韦后喷昔洛韦的平均尿回收率和肾清除率值分别为56.8%和27升·小时-1,与别嘌醇合用时分别为59.7%和27.5升·小时-1。两种药物合用未发现喷昔洛韦无活性前体BRL 42359蓄积的证据。别嘌醇与泛昔洛韦合用时,别嘌醇的平均稳态Cmax、AUC和终末相半衰期值与单独服用别嘌醇后获得的值相比似乎也未改变,分别为2.12微克·毫升-1、5.73微克·小时·毫升-1和1.38小时。别嘌醇活性代谢产物氧嘌呤醇的平均Cmax和AUC值分别为11.2微克·毫升-1和96.0微克·小时·毫升-1,与泛昔洛韦合用后这些值也未改变,分别为10.6微克/毫升和89.8微克·小时/毫升。(摘要截断于250字)