Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria Nsukka, Enugu Campus.
Faculty of Pharmaceutical Science, University of Port Harcourt, Rivers State, Nigeria.
Am J Ther. 2018 Jul/Aug;25(4):e397-e404. doi: 10.1097/MJT.0000000000000032.
The in vivo effects of norfloxacin (NXC) and ofloxacin (OXC) on isoniazid (INH) pharmacokinetics were investigated in 5 apparently healthy volunteers aged 18-39 years after an informed consent. The study was carried out in 3 phases with an interval drug wash out period of at least 1 week in between the phases. In phase 1 (INH alone), subject received 300 mg (usual adult dose) of INH. In phase 2 (INH + OXC), 300 mg of INH was coadministered with 200 mg of OXC, and in phase 3 (INH + NXC) each received 300 mg of INH together with 400 mg of NXC after 1-week drug wash period. Drugs were taken orally with 350 mL of water after an overnight fast, and the subject fasted 3 hours after drug. Plasma, saliva, and urine concentration of INH were predetermined at zero hour, then hourly until the eighth hour, 12 hours, 24 hours, and finally at 48 hours. The urine samples were further collected at 72 hours after drug(s) administration using validated methods. Various pharmacokinetics parameters were calculated. Various pharmacokinetic parameters of INH significantly differed when administered alone or in combination with OXC or with NXC. The mean saliva to plasma ratio of INH concentration was 0.14. The bioavailability indices of INH in the saliva and plasma were similar in all the groups. NXC and OXC reduced the extent and rate of absorption of INH. The determination of INH levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies.
在知情同意后，我们在 5 名年龄在 18 至 39 岁的健康志愿者中研究了诺氟沙星（NXC）和氧氟沙星（OXC）对异烟肼（INH）药代动力学的体内影响。该研究分 3 个阶段进行，每个阶段之间至少有 1 周的药物洗脱期。在第 1 阶段（单独使用 INH），受试者接受 300mg（成人常用剂量）INH。在第 2 阶段（INH+OXC）中，300mg INH 与 200mg OXC 共同给药，在第 3 阶段（INH+NXC）中，在经过 1 周的药物洗脱期后，每位受试者接受 300mg INH 和 400mg NXC。药物在禁食过夜后用 350mL 水口服，受试者在药物后 3 小时禁食。在零时，然后每小时一次，直到第八小时、十二小时、二十四小时，最后在四十八小时，测定 INH 的血浆、唾液和尿液浓度。在药物（s）给药后 72 小时，使用验证方法进一步收集尿液样本。计算各种药代动力学参数。当单独或与 OXC 或 NXC 联合使用时，INH 的各种药代动力学参数有显著差异。INH 浓度的唾液与血浆比的平均值为 0.14。唾液和血浆中 INH 的生物利用度指数在所有组中相似。NXC 和 OXC 降低了 INH 的吸收程度和速度。唾液中 INH 水平的测定可能有助于治疗药物监测和药代动力学研究。
