INFLUENCE OF CIMETIDINE ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY SUBJECTS
INFLUENCE OF CIMETIDINE ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY SUBJECTS
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Date
1998-08
Authors
BALA, HINA AHMED
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Abstract
Considering the prevalence of peptic ulcer diseases in Nigeria and the popularity of
paracetamol as an "household" analgesic, there is the possibility of patients being
treated for peptic ulcer to take paracetamol. It is therefore possible for the drug(s)
used in the peptic ulcer treatment to influence the pharmacokinetic parameters of
paracetamol.
The influence of cimetidine (400mg) on the pharmacokinetics of oral single dose (1g)
paracetamol was studied in 8 healthy subjects under two protocols (concomitant and
delayed paracetamol administration 1 hour after cimetidine). The study was carried
out in 3 phases: paracetamol alone (control); paracetamol and cimetidine
concomitantly; and paracetamol 1 hour after cimetidine. A wash-out period of 2
weeks was allowed between the phases of the study. The method of residuals was
used to obtain the pharmacokinetic parameters using the salivary concentration-time
curves generated from the salivary concentration-time data as preliminary data.
Statistical analysis was done by the student two-tailed t-test of paired data.
Following the single oral one gram dose of paracetamol, the relevant mean
pharmacokinetics parameters obtained were in agreement with those in the established
literature.
For the influence of cimetidine on paracetamol, there were no significant changes
(P<0.10) when compared to the control in the salivary pharmacokinetics of
paracetamol
when the two drugs were concomitantly administered. Delayed administration of
paracetamol 1 hour after cimctidine, on the other hand, was associated with significant
changes in the pharmacokinetic parameters. The peak salivary concentration (Cmax)
and absorption rate constant (Kab) were significantly reduced (P<0.05), while the time
to peak concentration (Tmax),
absorption half-life (t1/2ab) and lag time were all significantly increased (P<0.05).
Elimination half life (t1/2el) and area under the curve (AUC o - oc) were significantly
increased (P<0.05 and 0.10 respectively). Elimination rate constant (Kel) and
clearance (C1) were significantly reduced (P<0.05 and 0.10 respectively). While
Volume of distribution (Vd) was significantly increased (P<0.05).
These findings indicated that cimetidine does not affect the pharmacokinetics of
paracetamol when the two drugs were concomitantly administered but impaired the
absorption and inhibited the metabolism of paracetamol when the administration of
the latter was delayed by 1 hour after cimetidine. The therapeutic implications of this
interaction is that the efficacy of paracetamol may be affected when the two drugs arc
used in combination.
Description
A THESIS SUBMITTED TO THE POSTGRADUATE SCHOOL, AHMADU BELLO
UNIVERSITY, IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE
AWARD OF MASTER OF SCIENCE
DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL CHEMISTRY
FACULTY OF PHARMACEUTICAL SCIENCES
AHMADU BELLO UNIVERSITY
ZARIA, NIGERIA
Keywords
INFLUENCE,, CIMETIDINE,, PHARMACOKINETICS,, PARACETAMOL,, HEALTHY SUBJECTS.