No abstract

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.

The in vivo effects of norfloxacin (NXC) and ofloxacin (OXC) on rifampicin (RIF) pharmacokinetics were investigated in 5 apparently healthy volunteers aged 18-39 years after informed consent. The study was carried out in 3 phases with an interval drug washout period of at least 1 week in between the phases. In phase 1 (RIF alone), the subject received 600 mg of RIF. In phase 2 (RIF + OXC), 600 mg of RIF was coadministered with 200 mg of OXC. In phase 3 (RIF + NXC), each subject received 600 mg of RIF together with 400 mg of NXC after 1 week drug washout period. Drugs were taken orally with 350 mL of water after an overnight fast, and the subjects fasted 3 hours after the administration of drug. Plasma, saliva, and urine concentration of RIF were predetermined at 0 hour and then hourly until the 8th, 12th, 24th, and 48th hour. The urine samples were further collected at 72 hours after drug(s) administration using validated methods. Various pharmacokinetics parameters were calculated. NXC reduced the extent and rate of absorption of RIF. Various pharmacokinetic parameters of RIF significantly differ when administered alone or in combination with OXC and NXC. The mean saliva to plasma ratio of RIF concentration was approximately 0.15. The bioavailability indices of RIF in the saliva and plasma were similar in all the groups. Several pharmacokinetic parameters could be calculated using different body fluid concentrations of RIF. The determination of RIF levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies.

Objective of the resent study was to determine the effect of ofloxacin (OXC) on the pharmacokinetics of isoniazid (INH). Five healthy volunteers aged 18 – 39 years participated in this study after an informed consent. The study was carried out in two phases with an interval of one-week drug wash out period in between phases. In phase one (INH alone), each subject received 300mg of isoniazid (INH) with 350ml of water after an overnight fast. The subjects were made to fast 2 hours post drug. In phase two (INH + OXC), each subject was administered with 300mg of INH in combination with 200mg of OXC observing all the protocol in phase one. The concentration of INH in plasma, saliva and urine of the subjects at predetermined time intervals were measured spectrophotometrically in the two phases over a period of 0 - 48 hours. Various pharmacokinetics parameters were calculated. From the study it is evident that Ofloxacin (OXC) increased the rate and extent of absorption of isoniazid. The absorption half-life (t1/2a) and the maximum concentration and absorption time (Cmax, Tmax) of isoniazid (INH) were increased in the presence of OXC. The urinary excretion of isoniazid was also increased by ofloxacin. The salivary concentration of isoniazid was less than the corresponding plasma drug concentrations, a pattern also found in similar studies. Thus it can be concluded that Ofloxacin increases absorption kinetics and urinary excretion of Isoniazid.DOI: http://dx.doi.org/10.3329/icpj.v1i12.12449 International Current Pharmaceutical Journal 2012, 1(12): 403-409