THE EFFECTS OF CHLOROQUINE, PARACETAMOL AND PROMETHAZINE ON THE PHARMACOKINETICS OF CHLORPROPAMIDE IN HUMAN VOLUNTEERS
THE EFFECTS OF CHLOROQUINE, PARACETAMOL AND PROMETHAZINE ON THE PHARMACOKINETICS OF CHLORPROPAMIDE IN HUMAN VOLUNTEERS
No Thumbnail Available
Date
2008-03
Authors
DANLAMI, UZAMA
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The effect of chloroquine, paracetamol and Promethazine on the
pharmacokinetic profile of chlorpropamide was investigated in human
subjects.
The batches of chlorpropamide, chloroquine, paracetamol and
Promethazine used were subjected to quality control studies using official
methods. The drugs complied with the B.P (1993) requirements stated in
their monographs.
A high performance liquid chromatography (HPLC) method was developed
for the analysis of plasma chlorpropamide concentration. Pharmacokinetic
parameters of chlorpropamide were derived with Winnonlin standard noncompartment
software programme.
About 16%, 14% and 15% decrease in the mean maximum
concentration (Cmax) of chlorpropamide was observed following oral
administration of chlorpropamide with chloroquine, paracetamol and
Promethazine respectively.
About 44%, 11% and 30% decrease in the area under curve (AUC) of
chlorpropamide was observed following concurrent administration of
chlorpropamide with chloroquine, paracetamol and Promethazine
respectively. The plasma clearance of chlorpropamide increased by 86%
following chlorpropamide interaction with chloroquine.
The absorption half-life (t½a) of chlorpropamide increased by 4%, 85%
and 69% when concomitantly administered with chloroquine, paracetamol
and Promethazine respectively.
The elimination constant (Kel) of chlorpropamide was found to have
increased by 100% and decreased by 31% following concomitant
administration of chlorpropamide with chloroquine and paracetamol
respectively. The elimination half-life (t½el) of chlorpropamide was found to
have decreased by 47% and increased by 13% and 29% following
concomitant administration to chlorpropamide with chloroquine,
paracetamol and Promethazine respectively.
The study implied impaired absorption and elimination of chlorpropamide
by chloroquine, paracetamol and Promethazine.
Description
A DISSERTATION SUBMITTED TO THE POSTGRADUATE
SCHOOL IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE AWARD OF THE DEGREE OF DOCTOR OF
PHILOSOPHY IN PHARMACEUTICAL CHEMISTRY
DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL
CHEMISTRY
FACULTY OF PHARMACEUTICAL SCIENCES
AHMADU BELLO UNIVERSITY
ZARIA NIGERIA
MARCH 2008
Keywords
EFFECTS,, CHLOROQUINE,, PARACETAMOL,, PROMETHAZINE,, PHARMACOKINETICS,, CHLORPROPAMIDE,, HUMAN,, VOLUNTEERS