Published: 2019-04-23

Therapeutic drug monitoring of phenytoin using high performance liquid chromatography in a tertiary care hospital of Kashmir, India

Mohd Adil, Sameena Farhat, Mohd Younis Rather


Background: Phenytoin is the most commonly used anti-epileptic drug (AED) in this set up due to cost effectiveness and easy availability. Significant fluctuations in serum phenytoin levels leading to toxicities or treatment failures make it an ideal candidate for therapeutic drug monitoring (TDM).

Methods: Patients of age ≥18 years who were put on phenytoin were enrolled in this study. Estimation of serum phenytoin levels was done using HPLC. Data was analysed using SPSS version 20.0. Chi square test, Kruskal Wallis test were used to analyse the data.

Results: A total of 105 patients enrolled in the study, twenty patients (19%) had normal or therapeutic serum phenytoin levels. Thirty-nine patients (37.2%) had sub therapeutic serum phenytoin levels, while forty-six patients (43.8%) had toxic serum phenytoin levels.

Conclusions: The TDM of phenytoin should adopt a multi-disciplinary approach with active involvement of neuro-physicians, pharmacologists, pharmacists and other technical staff for improving the overall management of epilepsy. TDM data will provide the clinicians with greater insight into the factors determining the patient’s response to drug therapy.


Epilepsy, HPLC, Phenytoin, TDM

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Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Internal Med. 2009;24(1):1.

Rosemary J, Surendiran A, Rajan S, Shashindran CH, Adithan C. Influence of the CYP2CP and CYP2C19 polymorphisms on phenytoin hydroxylation in healthy individuals from south India. Ind J Med Res. 2006;123(5):665.

McNamara JO. Pharmacotherapies of the epilepsies. In: Brunton LL, Lazo JS, Parker KK, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw Hill; 2006: 501-526.

Krishnan A, Sahariah SU, Kapoor SK. Cost of epilepsy in patients attending a secondary‐level hospital in India. Epilepsia. 2004;45(3):289-91.

Krishnan RA, Chowdhury D. Cost of antiepileptic drugs in India. Neurol Asia. 2007;12(1):42-3.

Reynolds EH, Trimble MR. Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs. 1985;29(6):570-81.

Dodig S. Interferences in quantitative immunochemical methods. Biochem Med. 2009;19(1):50-62.

Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Therapeutic Drug Monitoring. 2018;40(5):526-48.

Dahiya K, Bansal P, Ghalaut VS, Dhankhar R, Ghalaut PS. Therapeutic drug monitoring for antiepileptic drugs using HPLC: an experience at a tertiary care hospital in India. Neurol Asia. 2010;15(3).:233.

Wu MF, Lim WH. Phenytoin: a guide to therapeutic drug monitoring. Proceedings Singapore Healthcare. 2013;22(3):198-202.

Lascelles PT, Kocen RS, Reynolds EH. The distribution of plasma phenytoin levels in epileptic patients. J Neurol Neurosurg Psychiatry. 1970;33(4):501-5.

Houghton GW, Richens A, Leighton M. Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients. Brit J Clin Pharmacol. 1975;2(3):251-6.

Garg SK, Gupta MC, Handu SS, Bhargava VK. Therapeutic drug monitoring of antiepileptic drugs-a preliminary experience. Ind J Pharmacol. 2000;32(1):28-30.

Lertsinudom S, Chaiyakum A, Tuntapakul S, Sawanyawisuth K, Tiamkao S. Integrated Epilepsy Research Group. Therapeutic drug monitoring in epilepsy clinic: a multi-disciplinary approach. Neurol Int. 2014;6(4).

Rasheva M, Staikov I. Low serum levels of antiepileptic drugs in patients with epilepsy-Bad compliance or something else. Austin J Clin Neurol. 2015;2(10):1083.

Travers RD, Reynolds EH, Gallagher BB. Variation in response to anticonvulsants in a group of epileptic patients. Arch Neurol. 1972;27(1):29-33.