STUDIES ON PHARMACOKINETICS AND SAFETY EVALUATION OF MELOXICAM WITH OR WITHOUT CO-ADMINISTRATION OF ANDROGRAPHOLIDE OR BROMELAIN IN RATS
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Date
2022
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KARNATAKA VETERINARY, ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR
Abstract
The present study was designed to evaluate the pharmacokinetic (PK) and
safety evaluation of meloxicam (MLX) with or without co-administration of
andrographolide (AGL) or bromelain (BRM) in Wistar rats. The pharmacokinetic
parameters of MLX in Group I (MLX @ 5 mg.kg-1, p.o.), II (MLX + AGL @ 60
mg.kg-1, p.o) and III (MLX + BRM @ 50 mg.kg-1, p.o) revealed no significant change
in observed Tmax of 4 h in all groups (n=8 per group). The PK parameters were
analyzed with High Performance Liquid Chromatography (HPLC) and calculated by
using PK SolverĀ®, version 2.0. The time vs concentration of MLX data was found best
fit in to noncompartmental model. The Cmax of MLX was decreased in Groups II, III
compared to Group I. The AUC of MLX was decreased in Groups II and III compared
to Group I. The half life of MLX was decreased in Group II, while it had increased in
Group III compared with Group I. For the safety evaluation study, the rats were
divided into six groups viz: I (control), II (MLX @ 10 mg.kg-1, p.o.), III (AGL @ 60
mg.kg-1, p.o.), IV (BRM @ 50 mg.kg-1, p.o.), V(MLX+AGL) and VI (MLX+BRM).
The haematological parameters viz: In Group II, haemoglobin, total erythrocyte count
and packed cell volume values were significantly decreased (p<0.05). Liver and
kidney function enzymes were increased significantly (p<0.05) in Groups II and VI
which was correlated by the histopathology. The study concluded that AGL coadministration
had no influence on pharmacokinetics of MLX, while BRM enhanced
the half-life of MLX, and there by enhanced the hepatic and renal damage potential of
MLX on co-administration indicating the herb drug interactions.
Key words: Meloxicam, Andrographolide, Bromelain, Pharmacokinetics, Safety,
Interactions