COMPARISON OF THE EFFECTS OF CIMETIDINE AND METHYLDOPA ON THE PHARMACOKINETICS OF PARACETAMOL IN HUMAN
COMPARISON OF THE EFFECTS OF CIMETIDINE AND METHYLDOPA ON THE PHARMACOKINETICS OF PARACETAMOL IN HUMAN
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Date
2009-03
Authors
IBRAHIM, Nurudeen Sani
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Abstract
Comparison of the effects of cimetidine and methyldopa were studied in 5 phases: via
phase I, ingestion of paracetamol 1g alone, phase II, administration of paracetamol 1g
and cimetidine 400mg concurrently, phase III administration of cimetidine 400mg
followed by paracetamol 1g after an hour, phase IV, ingestion of paracetamol 1g and
methyldopa 250mg concomitantly, phase V, administration of methyldopa 250mg
followed by paracetamol 1g an hour after. The protocol involves 8 healthy male
volunteers, non-smokers and non-alcoholic who fast overnight. Saliva samples were
usually collected after ingestion of the drugs for different phases at an interval of 0.25,
0.5, 1, 2, 3, 4, 5 hours for extraction and analysis. Analytical method was used to
determine paracetamol concentration using ultraviolent spectroscopic meter. The
method was validated for both; within day and between day processions with extract
recovery of 96%. The pharmacokinetic parameters for the five phases were determined
using a log transfer data, these are Cmax, Tmax, Kβ, Kα, t1/2α, t1/2α, t1/2 ,Cl, and Vd.
and AUC curves were used to generate pharmacokinetic parameters. The data
obtained were compared, with values of P > 0.05 considered to be statistically
significant. When cimetidine and paracetamol were concomitantly administered no
significant change was observed (P < 0.10) with values obtained when paracetamol was
administered alone (control), on the other hand when paracetamol was administered an
hour after cimetidine significant changes of pharmacokinetic parameters of paracetamol
were recorded and compared to the value of the control phase. In this phase
Paracetamol administration was analyzed by an hour after cimetidine ingestion. There
are so many changes observed compared to the phase one parameters obtained this is
as a result of possible drug interaction sequence to the inhibition of Paracetamol a
absorption by cimetidine it could be seen that there is considerable reduction in the
figures of Cmax and Kab by 36.45 % and 47.05% respectively (P< 0.05) which clearly
indicates that there is a reduction in the absorption of Paracetamol. Tmax, t½αand lag
time had significantly increased by 52.40% 52.5% and 43.78% respectively (P<0.050). It
was also observed that there are insignificant changes in the pharmacokinetic
parameters of paracetamol when paracetamol was administered with methyldopa
irrespective of time interval leading to a suggestion that there is no influence in the
pharmacokinetics of paracetamol by methyldopa. The findings indicate that on
comparison, cimetidine may influence the pharmacokinetics of paracetamol depending
on time of administration of the two drugs. While no change of pharmacokinetic
parameters observed when methyldopa was administered with paracetamol irrespective
of time interval.
Description
A THESIS SUBMITTED TO THE POSTGRADUATE SCHOOL AHMADU BELLO
UNIVERSITY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE
AWARD OF THE DEGREE OF MASTER OF SCIENCE IN
PHARMACEUTICALANLYSIS
DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL
CHEMISTRY,
FACULTY OF PHARMACEUTICAL SCIENCE,
AHMADU BELLO UNIVERSITY,
ZARIA, NIGERIA
Keywords
COMPARISON,, EFFECTS,, CIMETIDINE,, METHYLDOPA,, PHARMACOKINETICS,, PARACETAMOL,, HUMAN.