Teng R, Dogolo L C, Willavize S A, Friedman H L, Vincent J
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
J Antimicrob Chemother. 1997 Jun;39 Suppl B:87-92. doi: 10.1093/jac/39.suppl_2.87.
Two studies determined the oral bioavailability of trovafloxacin (CP-99,219) in healthy volunteers under fasted and fed conditions. In a randomized, two-way crossover study, 12 fasting subjects received two 100 mg tablets of trovafloxacin and an equivalent dose of alatrofloxacin (CP-116,517), administered by i.v. infusion over 1 h. Alatrofloxacin, the L-Ala-L-Ala prodrug of trovafloxacin, is rapidly converted in the body to trovafloxacin. After the oral dose of trovafloxacin, the mean Cmax and AUC were 2.2 mg/L and 30.4 mg x h/L, respectively. After the infusion of alatrofloxacin, the Cmax and AUC of trovafloxacin were 3.2 mg/L and 34.7 mg x h/L, respectively. The mean T(1/2) after both treatments was about 11 h. The mean Cl and Vd(ss) of trovafloxacin after the infusion of alatrofloxacin were 1.32 mL/min/kg and 1.13 L/kg, respectively. The mean oral bioavailability of trovafloxacin was estimated to be 87.6% (range 64.8-122.1%). Another randomized, open, three-way crossover study was conducted in 12 healthy male volunteers to investigate the effect of food in the gastrointestinal tract on the bioavailability of trovafloxacin. Each subject received three 100 mg tablets after fasting overnight (treatment A) or after a standard breakfast (treatment B), or 300 mg as oral aqueous suspension after fasting overnight (treatment C). Mean Tmax after treatment B occurred 2.2 h later (3.6 h vs 1.4 h) than after treatment A. Mean Cmax and AUC were 2.3 and 2.6 mg/L and 38.2 and 39.5 mg x h/L after B and A, respectively. About 5% of the administered dose was recovered unchanged in the 24 h urine sample after all three treatments. Thus, the food reduced mean Cmax by 12% but had no appreciable effect on mean AUC. The mean bioavailability of trovafloxacin administered as treatment regimen B was 96.6% relative to that of treatment A. The respective mean bioavailabilities of trovafloxacin as treatments B and A were 91.3% and 94.5% respectively of that of treatment C. The results of these studies indicate that trovafloxacin has good oral bioavailability and that the ingestion of food is unlikely to have a clinically significant effect on the bioavailability of trovafloxacin.
两项研究测定了曲伐沙星（CP - 99,219）在健康志愿者禁食和进食条件下的口服生物利用度。在一项随机、双向交叉研究中，12名禁食受试者接受了两片100毫克的曲伐沙星片剂以及等效剂量的阿拉曲伐沙星（CP - 116,517），后者通过静脉输注1小时给药。阿拉曲伐沙星是曲伐沙星的L - 丙氨酸 - L - 丙氨酸前药，在体内迅速转化为曲伐沙星。口服曲伐沙星后，平均Cmax和AUC分别为2.2毫克/升和30.4毫克·小时/升。输注阿拉曲伐沙星后，曲伐沙星的Cmax和AUC分别为3.2毫克/升和34.7毫克·小时/升。两种治疗后的平均T(1/2)约为11小时。输注阿拉曲伐沙星后曲伐沙星的平均Cl和Vd(ss)分别为1.32毫升/分钟/千克和1.13升/千克。曲伐沙星的平均口服生物利用度估计为87.6%（范围64.8 - 122.1%）。另一项随机、开放、三向交叉研究在12名健康男性志愿者中进行，以研究胃肠道中的食物对曲伐沙星生物利用度的影响。每位受试者在过夜禁食后（治疗A）或标准早餐后（治疗B）接受三片100毫克片剂，或在过夜禁食后接受300毫克口服水混悬液（治疗C）。治疗B后的平均Tmax比治疗A后晚2.2小时出现（3.6小时对1.4小时）。治疗B和A后的平均Cmax和AUC分别为2.3和2.6毫克/升以及38.2和39.5毫克·小时/升。所有三种治疗后，在24小时尿液样本中约5%的给药剂量未发生变化地被回收。因此，食物使平均Cmax降低了12%，但对平均AUC没有明显影响。作为治疗方案B给药的曲伐沙星的平均生物利用度相对于治疗A为96.6%。曲伐沙星作为治疗B和A的各自平均生物利用度分别为治疗C的91.3%和94.5%。这些研究结果表明，曲伐沙星具有良好的口服生物利用度，并且摄入食物不太可能对曲伐沙星的生物利用度产生临床显著影响。
