Effect of aceclofenac on pharmacokinetics of phenytoin sodium in epileptic patients

Authors

  • Rushikesh S. Kulkarni Department of Pharmacology, Swami Ramanand Teerth Government Rural Medical College, Ambajogai, Maharashtra, India
  • Kantilal C. Chandaliya Department of Pharmacology, Government Medical College, Aurangabad, Maharashtra, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20183922

Keywords:

Aceclofenac, Phenytoin sodium, Pharmacokinetics

Abstract

Background: Epilepsy is a chronic disorder characterised by recurrent seizures/convulsions that affects people of all ages. Phenytoin sodium is an effective, cheaper, most commonly used first line drug for the treatment of epilepsy. As a result of sure encounter with various painful inflammatory conditions like chronic arthritis at some point of time the co administration of analgesics becomes inevitable in epileptic patients. Aceclofenac is a commonly prescribed, moderately COX-2 selective congener of Diclofenac. Because of similarity in some pharmacokinetic properties between Phenytoin sodium and Aceclofenac; the possibility of drug interaction between them is postulated.

Methods: In this prospective randomized observational study diagnosed and stabilized patients of epilepsy of either sex of more than 18 years of age were included. Patient taking Phenytoin sodium 100mg BD and prescribed tab Aceclofenac 100mg bd for 7 days. Serum Phenytoin sodium levels were measured before and after administering Aceclofenac. Graph pad Prism software Version 6 used for statistical analysis.

Results: At the end of the study, we found statistically significant effect (p = 0.0104) on serum Phenytoin sodium level. However, no statistical difference was found in any of the other parameters i.e., epilepsy outcome parameters and lab parameters - Urine routine microscopy, CBC, LFT, KFT and RBG.

Conclusions: Findings in this study forms a platform for future researchers to explore this field of research by designing an interventional study with well scrutinised study population considering all pharmacokinetic parameters.

 

References

WHO. Media centre Epilepsy. Media Cent Epilepsy [Internet]. 2015;(Fact sheet N°999):10-3. Available at: http://www.who.int/mediacentre/factsheets/fs999/en/#. Accessed 3 June 2016.

Lowenstein DH. Section 2 Diseases of the Central Nervous System 445 445 Seizures and Epilepsy. In: Harrisons principles of internal medicine; 2015:2542-2559.

Vajda FJE, Eadie MJ. The clinical pharmacology of traditional antiepileptic drugs. Epileptic Disord. 2014;16(4):395-408.

Harivenkatesh N, Haribalaji N, David DC, Kumar CM. Therapeutic drug monitoring of antiepileptic drugs in a tertiary care hospital in India. Clin Neuropharmacol. 2015;38(1):1-5.

McNamara JO. Pharmacotherapy of the Epilepsies. In: Goodman and Gilman’s: The Pharmacological Basis of Therapeutics, 12e; 2011:583-606.

Tripathi K. Chapter 30 Antiepileptic Drugs. In: Essentials of Medical Pharmacology 7th Edition; 2013:411-424.

Blot L, Marcelis A, Devogelaer JP, Manicourt DH. Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage. Br J Pharmacol. 2000;131(7):1413-21.

Batlle-Gualda E, Román Ivorra J, Martín-Mola E, Carbonell Abelló J, Linares Ferrando LF, Tornero Molina J, et al. Aceclofenac vs paracetamol in the management of symptomatic osteoarthritis of the knee: a double-blind 6-week randomized controlled trial1, 2. Osteoarthr Cartil. 2007;15(8):900-8.

Moon Y, Kang S, Kim T, Lee M. Efficacy and Safety of Aceclofenac Controlled Release in Patients with Knee Osteoarthritis: A 4-week, Multicenter, Randomized, Comparative Clinical Study. Knee Surg Relat Res. 2014;26(1):33-42.

Richens A. Clinical Pharmacokinetics of Phenytoin sodium. Clin Pharmacokinet. 1979;4(3):153-69.

Neels HM, Sierens AC, Naelaerts K, Scharpé SL, Hatfield GM, Lambert WE. Therapeutic drug monitoring of old and newer anti-epileptic drugs. Clin Chem Lab Med. 2004;42(11):1228-55.

Bort R, Ponsoda X, Carrasco E, Mj G, Jv C. Metabolism of aceclofenac in humans. Drug Metab Dispos. 1996;24(8):834-41.

Drugs Update. Aceclofenac + Paracetamol information from Drugs Update. Available at: http://www.drugsupdate.com/generic/view/651/Aceclofenac-+-Paracetamol. Accessed 28 September 2017.

Medhi B, Joshi R, Prakash A, Bansal YS, Attrey SD, Singh D, et al. Effect of aceclofenac on pharmacokinetic of Phenytoin sodium. Pak J Pharm Sci. 2012;25(2):295-9.

Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004;10(2):307-12.

Recipe. Antiepileptics in Serum [Internet]; 2012. Available at: http://www.recipe.de/en/products_hplc_tdm_15000.html. Accessed 23 July 2017.

Fromm D. How do non-steroidal anti-inflammatory drugs affect gastric mucosal defenses? Clin Invest Med. Canada; 1987 May;10(3):251-8.

Chillistone S, Hardman JG. Factors affecting drug absorption and distribution. Anaesth Intensive Care Med [Internet]. Elsevier Ltd. 2014;15(7):309-13. Available at: http://dx.doi.org/10.1016/j.mpaic.2014.04.004. Accessed 30 July 2017

Sipponen P, Kekki M, Seppala K, Siurala M. The relationships between chronic gastritis and gastric acid secretion. Aliment Pharmacol Ther. England. 1996 Apr;10 Suppl 1:103-18.

Sigthorsson G, Tibble J, Hayllar J, Menzies I, Macpherson a, Moots R, et al. Intestinal permeability and inflammation in patients on NSAIDs. Gut. 1998;43(4):506-11.

Yanagawa A, Endo T, Kusakari K, Kudo T, Shimada J, Mizushima Y. Endoscopic evaluation of aceclofenac-induced gastroduodenal mucosal damage: a double-blind comparison with sodium diclofenac and placebo. Japa J Rheumatol. 1998 Sep 1;8(3):249-59.

Hinz B, Rau T, Auge D, Werner U, Ramer R, Rietbrock S, et al. Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003;74(3):222-35.

Sansom LN, Evans AM. What is the True Clinical Significance of Plasma Protein Binding Displacement Interactions? Drug Saf. 1995;12(4):227-33.

Nation RL, Evans AM, Milne RW. Pharmacokinetic drug interactions with Phenytoin sodium (Part I). Clin Pharmacokinet. 1990;18(1):37-60.

Aronson JK, Hardman M, Reynolds DJM. ABC of Monitoring Drug Therapy Phenytoin sodium. Br Med J. 1992;305(6863):1215 LP-18.

Barry M, Feely J. Enzyme induction and inhibition. Pharmacol Ther. 1990;48(1):71-94.

Downloads

Published

2018-09-24

How to Cite

Kulkarni, R. S., & Chandaliya, K. C. (2018). Effect of aceclofenac on pharmacokinetics of phenytoin sodium in epileptic patients. International Journal of Basic & Clinical Pharmacology, 7(10), 1912–1916. https://doi.org/10.18203/2319-2003.ijbcp20183922

Issue

Section

Original Research Articles