COMPARISON OF THE EFFECTS OF CIMETIDINE AND DIAZEPAM ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY HUMAN VOLUNTEERS
COMPARISON OF THE EFFECTS OF CIMETIDINE AND DIAZEPAM ON THE PHARMACOKINETICS OF PARACETAMOL IN HEALTHY HUMAN VOLUNTEERS
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Date
2006-12
Authors
RASHEED, Muazu Haruna
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Abstract
The influence of Cimetidine (400 mg) and Diazepam (5 mg) on the
pharmacokinetics of oral paracetamol (1000 mg) was studied and compared in
eight (8) healthy human under two (2) protocols; concomitant and delayed
administration of paracetamol. Subjects received one treatment at each of the five
sessions with a 2 weeks wash out period in-between. Paracetamol alone was used
as control. This was compared with concomitant administration with Cimetidine
and then delayed (l hour later) administration of paracetamol after Cimetidine.
Diazepam was used in phase IV and V under the same protocol of concomitant
administration with paracetamol and delayed administration of paracetamol l
hour of diazepam. Ultraviolet spectrophotometer was used to determine the
saliva concentration of paracetamol. Pharmacokinetic parameters (Kab, t1/2el, t1/2(ab),
Kel, Kab, lag time were determined by plotting paracetamol concentrations against
time on a logarithmic scale while other parameters were calculated.
There was no significant effect (p > 0.05) on the parameters on concomiittant
administration for both drugs (cimetidine and diazepam) when compared to the
control. However, on delayed administration of paracetamol 1 hour after
administration of diazepam, Tmax and lag time were greatly reduced 31.11 % and
50 % repectively P < 0.05. T1/2(ab) and Kel were significantly increased 48.42 %
and 54.57 % P < 0.05 respectively. The volume of distribution (Vd) and clearance
(Cl) were not significantly affected P > 0.05.
Delayed administration of paracetamol 1 hour after cimetidine affected all the
parameters Cmax and Kab were significantly reduced P < 0.05 by 30.02 % and 45.06 % respectively. While Tmax, t1/2(ab) and lag time were significant increased
(p < 0.05) by 47.97 %, 42.32 % and 60.13 % respectively.
Clearance (Cl) and Kel were reduced significantly (P < 0.05) by 20.75 % and
42,76 % respectively. T1/2(el) and AUC0 - ∞ were increased by 39.20 % and 29.08
% respectively. The above findings show that concomitant administration of
paracetamol + diazepam and of paracetamol + cimetidine does not cause any
effect on the kinetics of paracetamol. On the other hand, delayed administrations
of paracetamol one hour after cimetidine show decrease in absorption and
delayed elimination probably due to delay in gastric emptying and inhibition of
metabolism respectively.
Administration of paracetamol one hour after diazepam ingestion shows increase
in absorption and change in other pharmacokinetic parameters due to enhanced
gastric emptying and amplitude of contraction.
Description
A THESIS SUBMITTED TO THE POSTGRADUATE SCHOOL
AHMADU BELLO UNIVERSITYIN PARTIAL FULFILLMENT OF THE
REQUIREMENTS FOR THE AWARD OF MASTER OF SCIENCE IN
PHARMACEUTICAL CHEMISTRY
DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL
CHEMISTRY,
FACULTY OF PHARMACEUTICAL SCIENCES,
AHMADU BELLO UNIVERSITY,
ZARIA, NIGERIA
Keywords
COMPARISON,, EFFECTS,, CIMETIDINE,, DIAZEPAM,, PHARMACOKINETICS,, PARACETAMOL,, HEALTHY HUMAN VOLUNTEERS.