Isoniazid Pharmacokinetics in the Presence of Ofloxacin and Norfloxacin Antibiotics.
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.
Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria Nsukka, Enugu Campus.
Chikere A
CA
Anusiem
Faculty of Pharmaceutical Science, University of Port Harcourt, Rivers State, Nigeria.
Sinyeofori A
SA
Brown
Faculty of Pharmaceutical Science, University of Port Harcourt, Rivers State, Nigeria.
Ndidi A
NA
Ezejiofor
Faculty of Pharmaceutical Science, University of Port Harcourt, Rivers State, Nigeria.
Ebenezer
E
Barikpoar
Faculty of Pharmaceutical Science, University of Port Harcourt, Rivers State, Nigeria.
Orish E
OE
Orisakwe
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics*; D009643:Norfloxacin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D015242:Ofloxacin; D009643:Norfloxacin; D007538:Isoniazid