COMPARATIVE PHARMACOKINETICS OF SPARFLOXACIN IN GLIBENCLAMIDE TREATED AND UNTREATED DIABETIC RATS
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Date
2019-11-07
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COLLEGE OF VETERINARY AND ANIMAL SCIENCES, POOKODE WAYANAD
Abstract
Diabetes mellitus (DM) is an endocrine related metabolic diseases that result in
hyperglycaemia. In diabetes, patients are prone for multiple diseases. Hence to control
these complications diabetic patients use medications like antihypertensive drugs,
antiarrhythmic, antibiotics, and antiplatelet aggregant drugs along with the regular antidiabetic drugs. Diabetes can cause alteration in pharmacokinetics and
pharmacodynamics due to alteration in drug transporters like P-glycoprotein, along
with this multidrug usage may result in drug interactions. Hence the effect of alteration
in pharmacokinetics of drug and also the interaction kinetics has to be found out in
diabetes condition to ensure safe and effective use for the wellbeing of animals.
Sparfloxacin is a third generation fluoroquinolone antimicrobial agent which is having
activity against wide range of organisms. There are very limited studies related to
pharmacokinetics of drugs in diabetes condition. The current study was undertaken to
investigate the pharmacokinetic parameters of sparfloxacin in diabetic rats after oral
administration and also to study alteration in pharmacokinetic parameters of
sparfloxacin in glibenclamide treated diabetic rats when compared to control rats. The
analysis was carried out using RP- HPLC with the mobile phase of 1% aqueous acetic
acid and acetonitrile (20:80) on a phenomenex luna 5µ C18 column at the flow rate of
0.7 ml/min and column temperature of 300C. The photodiode array detector (PDA) set
to 280 nm was used for detection. The method was validated with respect to accuracy,
precision, specificity and linearity. The retention time obtained for sparfloxacin was
8.5 min. The recovery was found to be 87±1.547 % in spiked plasma sample. The
intraday precision with the co-efficient of variation ranged from 2.474 to 8.218 %. And
interday mean error ranged from 0.0035 to 0.0512. Control rats, HFD rats, diabetic rats
and glibenclamide treated rats were given sparfloxacin at the dose rate of 200 mg/kg
and blood was collected at different time intervals and was analysed using RP- HPLC.
Pharmacokinetics of orally administered sparfloxacin in control, HFD and diabetic rats
were fitted into two compartment model where as in glibenclamide treated diabetic rats
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the pharmacokinetics of sparfloxacin were fitted to non-compartment model. In HFD,
diabetic and glibenclamide treated diabetic animals, the maximum plasma
concentration achieved by sparfloxacin gradually decreased in the respective order.
The rate of absorption of sparfloxacin was maximum in diabetic rats than control rats
which may be due to 11.02 fold and 15.9 fold change down-regulation of intestinal
(colon) ABCB1a/mdr1a and ABCB1b/mdr1b genes expression. The rate absorption of
sparfloxacin from the intestine was somehow decreased when glibenclamide was coadministered, even though there was 42.79 fold and 25.86 fold change down-regulation
of intestinal (colon) ABCB1a/mdr1a and ABCB1b/mdr1b genes expression
respectively. Probable reasons may be the pre-enterocytic interaction of glibenclamide
with sparfloxacin as indicated by increased Tmax, decreased slope of absorption,
decreased AUC (0-t) and AUC (0-∞). The maximum plasma concentration achieved by
the drug is less in HFD rats group, diabetic rats group and glibenclamide treated
diabetic rats group due to higher apparent volume of distribution. Rate of elimination
in diabetic rats is faster, due to polyuria hence half-life of sparfloxacin is less in diabetic
rat. However, in glibenclamide treated diabetic rats the half-life is increased due to
slower rate of absorption of drug and correction of polyuria. In both diabetic rats and
glibenclamide treated diabetic rats group, maximum plasma concentration achieved by
sparfloxacin is decreased when compared to control rats. Sparfloxacin being an
antibiotic, depend on its attained plasma concentration for its pharmacodynamic
activity. From this it can be concluded that dose adjustment of sparfloxacin is required
in diabetes and in glibenclamide treatment, to attain effective therapeutic
concentration.