Abstract
Plasma concentrations and pharmacokinetics of phenacetin, a CYP1A2 substrate were determined in normal and experimentally induced inflamed rats by turpentine oil to know the role of inflammation on the pharmacokinetics of phenacetin and formation of its active metabolite (paracetamol) by CYP1A2 in wistar albino rats, weighing about 200–250 g that were randomly divided into two groups consisting six in each group. Rats in group I (control) received phenacetin (150 mg kg−1, PO) where as group II received phenacetin 12 h after induction of inflammation by turpentine oil (0.4 mL, i.m). Blood samples were collected from retro orbital plexus at pre-determined time intervals prior to and at 0.166, 0.33, 0.67, 1.5, 2, 4, 8 and 12 h post-administration of phenacetin. Plasma was separated and analyzed for phenacetin and its metabolite paracetamol by HPLC assay. Based on plasma concentrations of phenacetin and its metabolite paracetamol, the pharmacokinetic parameters were determined by compartmental methods. C max of phenacetin was significantly (p < 0.01) decreased to 19.50 ± 2.74 μg mL−1 in inflamed conditions compared to 38.13 ± 2.20 μg mL−1 obtained in normal rats. Except, for significant (p < 0.001) increase in volume of distribution at steady state (V dss) from 2.87 ± 0.37 to 8.03 ± 1.26 L kg−1 and increased the rate of absorption with shorter absorption half-life (t 1/2ka) for phenacetin in inflammation. None of the pharmacokinetic parameters of either phenacetin or its metabolite paracetamol were affected. It can be concluded that turpentine oil induced inflammation has no role on the activity of CYP1A2 in rats, as the plasma concentrations and pharmacokinetic parameters of paracetamol were found unaltered.
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Acknowledgments
We specially thank Bristol Myers Squibb India Private Ltd, Bangalore, India for financial support. We also thank the Departments of Veterinary Pharmacology & Toxicology and Veterinary Microbiology of Sri Venkateswara Veterinary University and Department of Zoology, Acharya Nagarjuna University Andhra Pradesh, India for providing the equipment and laboratories used in this investigation.
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Prasad VGNV: Nil, Vivek Ch: Nil, Anand Kumar P: Nil, Ravi Kumar P: Nil, Rao GS: Nil.
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Prasad, V.G.N.V., Vivek, C., Anand Kumar, P. et al. Turpentine oil induced inflammation decreases absorption and increases distribution of phenacetin without altering its elimination process in rats. Eur J Drug Metab Pharmacokinet 40, 23–28 (2015). https://doi.org/10.1007/s13318-013-0172-7
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DOI: https://doi.org/10.1007/s13318-013-0172-7