Pharmacokinetics of Chloroquine and Metronidazole in Rats

Abstract

The single oral dose pharmacokinetics of chloroquine (5mg/kg body weight) and metronidazole (7.5mg/kg body weight) were studied in rats' serum. Chloroquine and metronidazole concentrations were measured using highperformance liquid chromatography (HPLC) method developed earlier in our laboratory. The data were fitted into a WinNonlin standard non-compartmental programme. The Maximum serum concentration Cmax (µg/ml) of chloroquine was 5.70 ± 1.41 while that of metronidazole was 3.13  0.30, Time to peak concentration tmax was 1.00  0.00 (h) and that of metronidazole was 0.83 ± 0.27, Volume of distribution Vd (L) 1.33 ± 0.26 for metronidazole 2.39  0.28; Elimination half-life t1/2 (h) 10.05 ± 3.01 for metronidazole 4.05  0.46. The values were comparable with the works of other authors. Compounds that show very high activity in -vitro may not have in vivo activity, or may be highly toxic using in-vivo models due to undesirable pharmacokinetic properties, and toxicity may result from formation of reactive metabolites. This study assures the quality of the brands of the drugs and encouraged the use of animal model in determining pharmacokinetic properties especially in drug design.

Chloroquine, an Anti-Malaria Drug as Effective Prevention for Hantavirus Infections

“…One of the main reasons for this slow elimination is the pH-dependent liposomal entrapment mechanism ( Savarino et al., 2003 ; Hu et al., 2020 ). Although exact pharmacokinetics of chloroquine for hamsters are not known, the elimination half-time in rats is around 10 days ( Mustapha et al., 2015 ). Ten days is significantly shorter than the half-time measured in humans but still indicates a slow elimination, which could explain the chloroquine build-up.…”

Chromosomal Aberration and Histopathological Effect of Metronidazole-Induced Toxicity in Male Rat

“…the Reduction happen by two routes, The inactivation reduction of metronidazole to non-toxic amino stable derivative is oxygen insensitive (3) . during reduction activation the drug MTZ uptake electrons leading to form ring division and produced cytotoxic derivatives, this lead to the MTZ action as electron acceptor and prevent the force of proton motion lead to decreasing ATP formation, at the beginning the MTZ produced free radical (nitroso) and derivative of hydroxylamine the high affinity of oxygen for ethan MTZ from generates oxygen radicals which stimulate DNA strand breaks 1 (4,5) . This drug is highly metabolized in liver and excreted by kidney and less with feaces [2] , After absorbed by intestine canal and increased its concentration in tissues, will be metabolized highly in liver via oxidation and glucuronide formed and this highly water solubility than the Glucuronic acid is original substance and excreted via kidney and little amount with feaces (6) , significantly MTZ have capability in reduced the amount of colonic oxidative damage to proteins with no any effect on liver and on the glutathione levels along the bowel (7) .…”

The –NO2 vibrational spectra of metronidazole for analytical method development using Fourier Transform Infrared compared to the UV-VIS spectrophotometry

“…This active compound is still considered as a standard gold antibiotic [2]. Some antibiotics that have anaerobic activity must be compared with metronidazole both in terms of antimicrobial activity, pharmacokinetics and pharmacodynamics, side effect profiles, and in terms of financing [3]. To guarantee the quality, the benefits of the composition and safety of the use of these medicinal products, quality control is needed to avoid the possibility of circulating drugs having the quality that does not meet the requirements.…”