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.
Many drugs used in the therapeutic regimen for various ailments undergo metabolism via cytochrome P450 1A2 (CYP1A2), so the agents or conditions altering the expression and/or activity of this enzyme play a significant role in therapeutic efficacy/failure of its substrates. Though curcumin is reported to be an inhibitor of CYP1A2, influence of curcumin on the pharmacokinetics of CYP1A2 probe phenacetin in rats has not yet been published to the best of our knowledge. Hence an attempt has been made to investigate the same. Two groups of wistar albino rats were taken, of which, one group received curcumin at 400 mg kg -1 , per os (PO) followed by phenacetin (150 mg kg -1 , PO) and the other received only phenacetin. Plasma concentrations of phenacetin, a known CYP1A2 substrate and its metabolite paracetamol were determined by high performance liquid chromatography. Based on plasma concentrations, the pharmacokinetic parameters were determined by compartmental methods. Curcumin pretreatment significantly (P \ 0.05) decreased peak plasma concentration (C max ) of phenacetin in rats. None of the other pharmacokinetic parameters of either phenacetin or paracetamol were affected. To conclude, curcumin pretreatment decreases C max of phenacetin but has no role on the disposition kinetics of either phenacetin or its metabolite paracetamol in rats. This implies that single dose of curcumin has no effect on CYP1A2 mediated metabolism in rats.
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