Effect of aceclofenac on pharmacokinetic of phenytoin

Aceclofenac is presently most commonly prescribed analgesic for chronic pain and inflammatory conditions. In clinical practice, phenytoin and aceclofenac are used in a chronic condition of generalized seizure with concomitant chronic pain. Hence there are chances of drug-drug interaction because modulations of isoenzymes involved in metabolism of phenytoin and aceclofenac are CYP2C9/10 and CYP2C19. It is important to maintain the therapeutic level of phenytoin in plasma for effective control of seizure. So, the aim of the study was to determine the effect of aceclofenac on the pharmacokinetics of phenytoin in rabbits. In a parallel design study, phenytoin 30 mg/kg/day per oral was given daily for seven days. On day 7, blood samples were taken at various time intervals between 0-24 hours. In aceclofenac group, phenytoin was administered for seven days as above. On day 8, aceclofenac 14 mg/kg alongwith phenytoin 30 mg/kg/day was administered and blood samples drawn as above. Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated. In aceclofenac group, there was decrease in t[1/2]el than phenytoin group significant changes were observed in the pharmacokinetic parameters in aceclofenac treated group. These results suggest that aceclofenac alter the pharmacokinetics of phenytoin. Confirmation of these results in human studies will warrant changes in phenytoin dose or frequency when aceclofenac is co-administered with it

Safety and efficacy of vitamin-based antioxidant therapy in patients with severe acute pancreatitis: a randomized controlled trial

Oxidative stress plays a major role in the pathogenesis of pancreatitis. Antioxidant therapy in the form of high-dose vitamin has been used for the treatment of severe acute pancreatitis with equivocal results. We wished to evaluate the efficacy and safety of antioxidant [vitamin A, vitamin C, vitamin E] therapy in patients with severe acute pancreatitis. Setting and design: This was a single-center, prospective, randomized, open-label with blinded endpoint assessment study of antioxidant therapy, conducted in the emergency department attached to our hospital. Thirty-nine patients with severe acute pancreatitis were randomly assigned to antioxidant treatment group [n=19] or a control group [n=20] within 96 hours of developing symptoms. Patients in the antioxidant group received antioxidants [vitamin A, vitamin E, vitamin C] in addition to the standard treatment provided to both the groups for a period of 14 days. The primary outcome variable was presence of organ dysfunction at day 7. The secondary outcome variables were length of hospital stay, multiorgan dysfunction [MODS] at day 7, recovery at the end of 4 weeks, complications, and mortality. The change in markers of oxidative stress from baseline was also measured. We demonstrated no significant difference in organ dysfunction [P=1.0], MODS [P=0.8], and length of hospital stay [P=0.29] between the two groups. All the patients survived in the antioxidant-treated group, whereas two patients died in the control group. The change in the levels of malondialdehyde, superoxide dismutase, and reduced glutathione were not significantly different in the two groups at day 7. Univariate analysis showed marginal benefit with antioxidant treatment [P=0.034] in patients with severe acute pancreatitis. This randomized study demonstrates that there is no significant benefit from antioxidant therapy in patients with established severe acute pancreatitis