COMPARISON OF THE EFFECTS OF CIMETIDINE AND TRAMADOL ON THE DISPOSITION OF PARACETAMOL IN HEALTHY HUMAN VOLUNTEERS
COMPARISON OF THE EFFECTS OF CIMETIDINE AND TRAMADOL ON THE DISPOSITION OF PARACETAMOL IN HEALTHY HUMAN VOLUNTEERS
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Date
2006-08
Authors
IBRAHIM, GAMAWA ADAMU
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Abstract
The influence of cimetidine (400mg) and Tramadol (100mg) on the disposition of oral
single dose (1g) Paracetamol was studied and compared in 8 healthy human
volunteers under two protocols; concomitant and delayed paracetamol administration.
Subjects received one treatment at each of five sessions 2wk apart. Ingestion of
Paracetamol (1g) alone was used as control and compared with paracetamol
concentration on concomitant (with tramadol (100mg) and then cimetidine (1g)) and
delayed administration (1h 45mins after tramadol and 1h after cimetidine). Saliva
paracetamol concentrations were determined with UV-Spectrophotometer.
Pharmacokinetic parameters (kab, t1/2ab, kel, t1/2el and lag time), were determined
by plotting paracetamol concentrations against time on a logarithmic scale while other
parameters were calculated.
For the influence of cimetidine and tramadol on paracetamol when either of the drugs
was administered concomitantly with the paracetamol there were no significant
changes (P>0.05) when compared to the control.
On delayed administration of paracetamol 1h 45mins after tramadol however, Tmax
and t1/2ab were significantly (P<0.05) increased by 20.21% and 19.47% respectively
while kab was significantly (P<0.05) reduced by 25.88%. The other parameters were
not significantly affected (P>0.05).
Delayed administration of paracetamol 1hour after cimetidine on the other hand
affected all the pharmacokinetic parameters significantly. The (Cmax) and kab were
significantly reduced (P<0.05) by 31.38% and 50.24% respectively, while Tmax,
t1/2ab and lag-time were significantly increased (P<0.05) by 45.65%, 46.65% and
36.41% respectively. The t1/2el and AUCo-∞ were also significantly increased
(P<0.50) by 59.31% and 29.45% respectively. Clearance (cl) and kel on the other
hand were significantly reduced (P<0.050) by 21.90% and 59.74% respectively. The
volume of distribution (vd) was significantly increased by 47.30%.
These findings indicated that cimetidine and tramadol do not affect the
pharmacokinetics of paracetamol when either drug was taken concomitantly with
paracetamol. However, when paracetamol is administered 1h 45mins after tramadol
(100mg), there was a significant delay in the absorption of paracetamol, but the
elimination is not significantly affected. There is both impaired absorption and
inhibited metabolism of paracetamol when the administration was delayed 1 hour
after cimetidine.
Description
THIS IS TO CERTIFY THAT THE WORK REPORTED IN THIS
THESIS WAS CARRIED OUT BY ME UNDER THE
SUPERVISION OF DR. M. GARBA AND DR. (MRS) M.T.
ODUNOLA IN THE DEPARTMENT OF PHARMACEUTICAL AND
MEDICINAL CHEMISTRY, FACULTY OF PHARMACEUTICAL
SCIENCE, AHMADU BELLO UNIVERSITY, ZARIA.
THE WORKS OF OTHER INVESTIGATORS WERE
ACKNOWLEDGED AND REFERRED TO ACCORDINGLY. I
DECLARE THAT NO PART OF THIS THESIS HAS BEEN
SUBMITTED ELSE WHERE FOR THE PURPOSE OF A
DEGREE.
Keywords
COMPARISON,, EFFECTS,, CIMETIDINE,, TRAMADOL,, DISPOSITION,, PARACETAMOL,, HEALTHY,, HUMAN,, VOLUNTEERS