EFFECT OF RANITIDINE ON PHARMACOKINETIC PARAMETERS OF METRONIDAZOLE IN HEALTHY HUMAN VOLUNTEERS
EFFECT OF RANITIDINE ON PHARMACOKINETIC PARAMETERS OF METRONIDAZOLE IN HEALTHY HUMAN VOLUNTEERS
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Date
2018-02
Authors
MUHAMMAD, Inusa Babanladi
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Abstract
Pharmacokinetics is the study of the time course of drug movement in the body during
absorption, distribution, metabolism and elimination.Drug interactions are
pharmacodynamic, pharmacokinetic, or clinical responses to the administration of a
drugcombination that differs from the known effects of the individual drugs administered
alone. The clinicalconsequences of drug interactions may be antagonistic, additive,
synergistic, or idiosyncratic, resulting in treatmentfailure, increased pharmacologic effect, or
toxic reactions, which may be serious or fatal. Due to the fact that mostdrugs are detoxified
by the liver, the most important of the pharmacokinetic drug interactions involve
drugmetabolism usually entailing the induction or inhibition of the cytochrome P450
(CYP450) enzyme system which isresponsible for oxidative-reductive metabolism.
This study was undertaken to compare the effect of ranitidine on the pharmacokinetic
parameters of metronidazole in saliva sample of normal healthy human volunteers by
applying UV spectrophotometric analytical method for the estimation of metronidazole.This
was done by preparing different concentrations of pure metronidazole in 0.1 N HCl
solutions and their respective absorbance determined at 277 nm. Quality control studies
(identification test, assay test, weight variation, friability test, disintegration and dissolution
rate) for both ranitidine and metronidazole were carried out according to BP2009. The
method of Kolawole and Ameh, 2004 was adopted and validated based on ICH guideline for
this study. Both metronidazole and ranitidine tablets passed all the quality control studies
and were thus found to be fit for the purpose of this study.The percentage recovery of the
method was within the accepted range of 98 – 102 %. Calibration curve was linear within
the range of 2.5–15 µg/ml adopted and validated. The adopted method was then employed in
determining the effect of ranitidine on the pharmacokinetics parameters (Cmax, Tmax, Kab, Kel,
t1/2ab, t1/2el, Cl, Vd, lag time and AUC) of metronidazole using human volunteers of 30 years
and above and the study was divided into three phases with a washout period of two weeks.
Both metronidazole and ranitidine used for this study were found to have the labeled active
ingredient.They all passed the assay test as they were within the acceptable limits 95 – 105
%. Weight variation was conducted for both metronidazole and ranitidine and they all
passed as their percentage mean deviation was less than 5 %. Similarly, both drugs passed
the friability test which was less than 1%. Disintegration tests for both drugs reveals that
they disintegrate in less 15 mins and also both metronidazole and ranitidine passed the
dissolution rate as more than 70 % of the active ingredient was released in 30 mins. The
percentage recovery of the method was within the accepted range of 98 – 102 %. Calibration
curve was linear within the range of 2.5 – 15 µg/ml as the correlation coefficient was
0.9681. The regression equation was y= 0.027x + 0.002. After concurrent and delayed
administration, Cmax of metronidazole was found to be statistically significant (p<0.05) at a
value of 51.57 μg/ml and 36.27 μg/ml. Other pharmacokinetic parameters of metronidazole
like AUC were not significantly (p < 0.05) affected by ranitidine. This finding indicates that
ranitidine may influence the pharmacokinetics of metronidazole when co-administered
together depending on the time of administration of the two drugs. Based on the finding the
dosage of the metronidazole has to be reduced when concurrently administered with
ranitidine so as to overcome the problem of toxicity due to significant increase of the drug in
the systemic circulation.
Description
A DISSERTATION SUBMITTED TO THE SCHOOL OF POSTGRADUATE
STUDIES, AHMADU BELLO UNIVERSITY ZARIA, NIGERIA
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF
MASTER OF SCIENCE DEGREE IN PHARMACEUTICAL CHEMISTRY
DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL CHEMISTRY,
FACULTY OF PHARMACEUTICAL SCIENCE,
AHMADU BELLO UNIVERSITY,
ZARIA-NIGERIA
Keywords
EFFECT OF RANITIDINE,, PHARMACOKINETIC PARAMETERS,, METRONIDAZOLE,, HEALTHY HUMAN VOLUNTEERS