Effect of Ofloxacin and Norfloxacin on Rifampicin Pharmacokinetics in Man

Abstract

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.

Systematic Review of Salivary Versus Blood Concentrations of Antituberculosis Drugs and Their Potential for Salivary Therapeutic Drug Monitoring

“…In general, a large variability in saliva–plasma and saliva–serum was observed for isoniazid, rifampicin, moxifloxacin, ofloxacin, and clarithromycin (Figures 2 and 3). The saliva–plasma and saliva–serum ratios of rifampicin were clustered in 2 groups: Murthy and Kumar, 28 Darouiche et al, 29 Ezejiofor et al, 30 and Gurumurthy et al, 31 with ratios of 0.1–0.2, in contrast to Orisakwe et al, 32 and Orisakwe and Ofoefule 33 with ratios around 0.6. A similar clustering effect was seen with moxifloxacin.…”