甲磺酸培氟沙星(Pefloxacin)正常人药代动力学研究

PHARMACOKINETICS OF PEFLOXACIN IN NORMAL VOLUNTEERS

八名男性健康志愿者交叉口服甲磺酸培氟沙星(甲氟哌酸)片剂和原粉水溶液各400mg,进行药代动力学试验。血浆和尿标本同时用微生物法和HPLC法进行测定,药代动力学数据用3P87程序处理。两种剂型吸收均有迟滞时间,但吸收较快。用微生物法和HPLC法测得片剂的峰浓度分别为5.78(±0.39)和6.03(±0.80)mg/l;达峰浓度时间分别为1.37(±0.24)和1.40(±0.80)h;吸收迟滞时间(tlag)分别为0.28(±0.17)和0.27(±0.04)h。口服水溶液的峰浓度与片剂相似,但达峰时间明显短于片剂,与水溶液相比,片剂吸收完全。口服两种剂型的药时曲线均符合二室模型。表观分布容积大于总体液,不同方法测得V/F值为46.60(±3.27)—52.31(±8.98)1,提示可在组织中较好地分布。该药消除较慢,消除速率常数较小,不同方法测得β值为0.0449(±0.0034)—0.0529(±0.0020)h^(-1),消除半衰期较文献报道的值长,不同方法测得为13.80(±0.68)—16.09(±1.27)h,如按文献报道的给药方法,每12h给药400mg,应注意蓄积倾向。该药原型尿中回收率较低,片剂和水溶液分别为给药剂量的23.48(±7.04)和18.53(±3.20)%,表明非肾消除为其主要消除途径。用微生物法测得两种剂型尿中回收剂量远高于HPLC法。片剂和水溶液分别为给药剂量的46.04(±7.02)和43.51(±6.99)%,此为原型药物和活性代谢产物氟哌酸的总量。尿中药物浓度高且维持时间长,利于尿路感染的治疗。

Single-dose pharmacokinetics of pefloxacin was studied in 8 normal male volunteers given crossly 400mg pefloxacin in tablet and in solution.Plasma and urine levels of pefloxacin were measured by both bioassay andhigh performance liquid chromatography. Pefloxacin in both formulationswas rapidly absorbed from the gastrointestinal tract wiht a short lag time,but its absorption in solution was faster than in tablet. The maximumplasma concentrations (Cmax ) after administration of tablets were 5.78(±0.39) mg/l at 1.37 (±0.24) h and 6.03 (±0.80) mg/l at 1.40 (±0.20)h from bioassay and HPLC, respectively. The Cmax after administrationof Solution was similar to that of tablet, but the peak time was signific-antly shorter than that of tablet. Pefloxacin tablet was completely abso-rbed after oral administration. The level-time curves of the both formula-tions fitted a two-compartment model. Pefloxacin elimination after admin-istration of tablet was slow. The t1/2β were 16.09 (±1 .27) and 14.73(±1. 61 ) from bioassay and HPLC, respectively. Similar results were obtained after administration of solution. Attention to pefloxacin cumulationin the body should be paid when patients repeatedly take it for a longperiod. The recoveries of unchanged pefloxacin in the both formulationswere 23.48 (±7.02) and 18.53 (±3.20) % of the dose, respectively, andrenal clearance of it were low (1. 10± 0. 48 and 0. 98± 0. 32 1/h, respectively),indicating that non-renal clearance represents the major route of elimination of this quinolone.