Chronic Effect of Gabapentin on Liver function in Adult Male Rats
Gabapentin (GPN) is a new antiepileptic agent currently in used as add-on therapy in adult patients suffering from partial seizures. The extent of liver damage at different dosage and long term treatment with GPN is not yet clear. Therefore this study was undertaken to find out the possibility of liver damage by this drug. Adult male (Wistar) rats of 180-220 g were administered intraperitoneally with GPN (20 or 100 mg/kg) for 45 days. After the experimental period, the liver function tests were carried out in control and experimental groups. The activity of liver enzymes, with 20 mg/kg of GPN were not significantly different from the control group but, the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, direct bilirubin and total bilirubin were enhanced significantly with 100 mg/kg of GPN. Total protein and albumin decreased in this group as compared with control animals. The histopathology of the liver parenchymal cells also showed minute foci of necrosis in a few rats treated with high dose of GPN, whereas, at therapeutic dose the histopathology and biochemical indices showed almost normal values. At therapeutic dose GPN is a safer drug with regards to liver function and hepatocellular damage as compared with other antiepileptic drugs.
Meshkibaf MH, Subhash MN, Rama Rao BSS, Narayanan CP, Kailashnath KM. Comparative effect of single and poly therapy on liver enzymes in epileptic patients under long-term treatment. Nimhans J 1995;141-6.
Patsalos NP. New antiepileptic drugs. Ann Clin Biochem 1999;36(Pt 1):10-9.
Harmuth-Hoene AE, Schelenz R. Effect of Dietary Fiber on Mineral Absorption in Growing Rats. Fed Res Cen. J NutR 1980;110(9) 1774-84.
Laxer KD. Guidline for treating epilepsy in the age of felbamate, vigabatrin, lamotrigine, and gabapentin. West J Med 1994;161(3):309-14.
Sutton KG, Martin DJ, Pinnock RD, Lee K, Scott RH. Gabapentininhibit high-threshold calcium channel currents in cultured rat dorsal root ganglion neurons. Br J pharmacol 2002;135(1):257-65.
McLean MJ. Gabapentin. Epilepsia. 1995;36(Supple2):S73-86.
Wilson EA, Sill GJ, Forrest G, Brodie MJ. High dose gabapentin in refractory partial epilepsy: clinical observations in 50 patients. Epilepsy Res 1998;29(2):161-6.
Preece N.E, Jackson GD, Houseman JA, Duncan JS, Williams SR. Nuclear magnetic resonance detection of increased GABA in vigabatrin-treated rats in vivo. Epilepsia 1994;35(2):431-6.
Beghi E, and Dimascio R. Antiepileptic drug toxic definition and mechanism of action. Neurol Sci 1986;7(2):209-22.
10. Mullick FG, Ishak KG. Hepatic injury associated with diphenyl-hydantion therapy: A clinicopathological study of 20 cases. Am J. Clin. Pathol 1980;74(4):442-52.
Arai YC, Matsubara T, Shimo K, Suetomi K, Nishihara M, Ushida T, Kobayashi K, Suzuki C, Kinoshita A, Kondo M, Matsubara S,Hayashi R, Tohyama Y, Nishida K, Arakawa M. Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine. J Anesth 2010;24(3):407-10.
Charles E Richardson. Gaqbapentin indused cholestasis. Br Med J 2002;325(7365):635.
Rosner H,Rubin L, Kestenbaum A. Gabapentin adjusnctive therapy in neuropathic pain states. Clin J Pain1996;12(1):56-8.
Patsalos PN, Duncan JS. Antiepileptic drugs: a review of clinically significant drug interactions. Drug Saf 1993;9(3):158-84.
Patsalos PN. Phenobarbitone to gabapentin: aguid to 82 years of anti-epileptic drug pharmacokinetic interactions. Seizure 1994;3:163-70.
Beydoun A, Fakhoury T, Nasreddine W, Abou Khalil B. Conversion to high dose Gabapentin monotherapy in patients with medically refractory partial epilepsy. Epilepsia 1998;39:188-93.
Sivenius J, Kalviainen R, Ylinen A, Riekkinen P. Doubleblind study of Gabapentin in the treatment of partial seizures. Epilepsia 1991;32:539-42.
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