Wael Abu Dayyih
University of Petra, Jordan
Title: Validation and determination of macrolides as clarithromycin and metronidazole in rat plasma using high performance liquid chromatography/mass-spectrometry in presence of pomegranate beverage
Biography
Biography: Wael Abu Dayyih
Abstract
Clarithromycin is Macrolides. is a semisynthetic 14-membered ring macrolide antibiotic. Clarithromycin binds to the 50S ribosomal subunit and inhibits RNA-dependent protein synthesis in susceptible organisms.
Metronidazole is a Nitro- imidazole Antimicrobial. The chemical classification of metronidazole is Nitro-imidazole. Metronidazole is a synthetic nitro-imidazole derivative with antiprotozoal and antibacterial activities.
The pomegranate (Punica granatum) is a fruit-bearing deciduous shrub or small tree in the family Lythraceae that grows between 5 and 10 m (16 and 33 ft.) tall
A simple, reproducible and rapid analytical method by using high performance liquid chromatography-mass spectrometry (HPLC/MS) with high resolution and sensitivity for simultaneous quantification of Clarithromycin and Metronidazole in presence of pomegranate juice was validated. A gradient mobile phase system consisting of methanol and 0.1% of formic acid and ACE 5 C18 column (50 X 2.1 mm, 5μ) were used with a flow rate of 1.0 ml/ min.
An acceptable recovery was achieved (97.75%) and (96.0%) for Clarithromycin and Metronidazole, respectively, with good accuracy and precision. Coefficient of determination (R²) of the standard curves for both drugs ranged between 0.9986 and 0.9998.
According to results obtained, there was no significant effect on pharmacokinetic parameters of Clarithromycin after pre-treatment with single and multiple doses of pomegranate fresh juice. However, there was two hours-long delay on T-max after the single dose of juice which is possibly with no clinically significant. Furthermore, the changing in t½ and the elimination rate constant of Clarithromycin after single and multiple pomegranate juice administration gives an expectation that pomegranate juice could affect the hepatic-mediated metabolism of Clarithromycin but with insignificant manner.
Pharmacokinetic parameters of Metronidazole were not affected by single dose administration of juice, on the other hand, multiple dose pre-treatment with juice significantly elevating the maximum plasma concentration (C-max) (PË‚0.05) and the area under the curve (AUC) of Metronidazole (P=0.001). Since there was a very slight changing on the t½ and the elimination rate constant, the hepatic enzymes could not be affected. In contrast, concomitant administration of Metronidazole and Clarithromycin showed no significant interaction.
Since there are different enteric metabolic enzymes involved in the orally administered drug metabolism, further in vitro and in vivo investigations to study the mechanism of the pomegranate juice effect on the pharmacokinetic parameters of these drugs should be established.