Author : Mona El Assal
CoAuthors : Mona Ibrahim Abdel tawab ElAssal and sally Ali Helmy
Source : Iranian Journal of Pharmaceutical Research (
Date of Publication : 11/2017
Abstract :
Co-administration of norfloxacin (NFX) and tinidazole (TNZ) has been used for the
treatment of gastrointestinal and urinary tract infections. Concomitant oral administration
of NFX with TNZ may affect NFX absorption and consequently its blood concentration and
pharmacological effect. The present study was undertaken to investigate the effect of TNZ at
the usual clinical dosage on the pharmacokinetics of NFX in healthy volunteers. This study
was conducted as an open-label, randomized, two-way crossover experimental design. After
an overnight fast, subjects were randomized to receive a single oral dose of NFX 400 mg
alone and the fixed-dose combination (FDC) of NFX /TNZ 400 mg/600mg on two different
occasions separated by 1 week washout period between treatments. Blood samples were
collected up to 24 h postdose, and plasma was analyzed for NFX concentrations by using
HPLC. The pharmacokinetic properties of NFX after FDC administration were compared with
NFX administered alone. Twelve healthy subjects were enrolled (6 in each part), and all subjects
completed the study. None of the participants showed any sign of adverse drug reactions during
or after the completion of the study. The 90% confidence interval (CI) between NFX alone and
when co-administered with TNZ indicated the presence of an interaction between NFX and
TNZ, which would significantly increase the systemic rate and exposure of NFX absorption.
The co-administration of TNZ with NFX increased the AUC and Cmax of NFX significantly
compared with administration of NFX alone. The AUC and Cmax of NFX alone were 6.0 μg.hr/
mL (2.3-9.8) and 0.87 μg/mL (0.4-1.6), respectively whereas the corresponding AUC and Cmax
values after administration of FDC were 7.1 μg.hr/mL (4.0-10.6) and 0.97 μg/mL (0.4-1.7),
respectively. The respective geometric mean ratios of NFX for AUC and Cmax with TNZ were
1.197 [90% CI, 0.941-1.522] and 1.087 (90% CI, 0.807 -1.463) compared with NFX alone.
Both Tmax and Ka of NFX showed a significant decrease after administration of the combination
compared to administration of NFX alone. The peak plasma concentration reached at 1.3 h
(0.6-2.4) and 1.9 h (0.4-4.4) after oral administration of FDC and NFX alone, respectively.
Both NFX and TNZ were well tolerated. The interaction of TNZ with fluroquinolones
should be investigated to determine whether this interaction is limited to NFX or if other
fluroquinolones have the same pharmacokinetic interactions. Further studies are necessary to
determine the role of P-gp and other transporters on NFX disposition and pharmacokinetics.
Additionally, the influence of TNZ on the physiological activity of GIT should be investigated.
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