INFLUENCE OF MEALS ON THE BIOAVAILABILITY AND PHARMACOKINETIC PROFILES OF CHLORPROPAMIDE IN MAN
INFLUENCE OF MEALS ON THE BIOAVAILABILITY AND PHARMACOKINETIC PROFILES OF CHLORPROPAMIDE IN MAN
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Date
1992-06
Authors
BAKARE, MOJIRADE TAIBAT
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Abstract
The effects of three different Nigerian meals on the
bioavailability and pharmacokinetic profiles of
chlorpropamide were studied in healthy subjects and in
freshly diagnosed Type II diabetic patients. The batch of
chlorpropamide tablets and the meals used were pre—analyzed
using official methods- The tablets complied with the B.P.
(1988) requirements stated under the monograph for
chlorpropamide and the meals contained high carbohydrate
contents of 80.5%, 76.0% and 84.5% for maize, cassava and
yam flour meals respectively.
Plasma levels of chlorpropamide were determined using
HPLC method. In addition, glucose levels were measured by a
standard glucose oxidase method (Martinek, 1964). Higher
levels of chlorpropamide were observed when the drug was
administered in fasting state compared with concomitant
administration of drug with maize, and cassava flour meals.
Concomitant administration of the drug with yam flour meal
however increased chlorpropamide levels in healthy subjects
and had no effect on chlorpropamide levels in diabetic
patients. Significantly lowered postprandial plasma glucose
increments were observed when 250mg chlorpropamide tablet
was taken with each meal than when each meal was taken
alone, and the glucose levels were even lowered when the
drug was taken 30min prior to meal ingestion compared with
when the drug was taken concomitantly with each meal. No
significant postprandial plasma glucose increments were
observed in healthy subjects.
The pharmacokinetic parameters were calculated by a
computer programme KINEMP1 Administration of
chlorpropamide concomitantly with each meal compared with
the fasting state affected some absorption parameters
(lagtime, tmax, Cmax, ka and tl/2x), the extent of
absorption, volume of distribution and the elimination
parameters calculated in this study were not significantly
affected by any of the meals. Some pharmacokinetic
parameters (lagtime, Cmax, tmax, ka, tl/2x and Vd)
calculated for the healthy subjects and diabetic patients
were significantly different. There was a relationship
between the hypoglycaemic responses and chlorpropamide
levels attained after administration of the drug to healthy
volunteers but no direct relationship was found for the
patients. Lower and statistically significant levels of
chlorpropamide were detected in saliva compared with the
plasma. The saliva and plasma (S/P) ratio was less than
unity at each sampling point and there was a correlation
between the saliva and plasma concentratons of chlorpropamide
measured.
Description
A THESIS SUBMITTED TO THE POSTGRADUATE SCHOOL,
AHMADU BELLO UNIVERSITY, ZARIA IN PARTIAL
FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD
OF THE DEGREE OF
DOCTOR OF PHILOSOPHY
DEPARTMENT OF PHARMACEUTICAL AND MEDICINAL
CHEMISTRY, FACULTY OF PHARMACEUTICAL SCIENCES,
AHMADU BELLO UNIVERSITY,
ZARIA
JUNE, 1992
Keywords
INFLUENCE,, MEALS,, BIOAVAILABILITY,, PHARMACOKINETIC,, PROFILES,, CHLORPROPAMIDE,, MAN.