Abstract
Objectives: To study serum concentration of carbamazepine and phenytoin, when given singly and together.
Method: This is a non-interventional, cross-sectional, analytical study done in a tertiary care hospital. Consenting epileptics on stable antiepileptic regime for at least past 2 weeks and taking carbamazepine 200mg BD (group I) or phenytoin 100mg BD (group II) or carbamazepine (200)+phenytoin (100)mg BD (group III) were included. There were 20 patients in each group. Blood samples were collected 12 hours after the last dose and serum was analyzed for carbamazepine, phenytoin concentrations using HPLC method and data was compared using unpaired t-test.
Results: Mean serum carbamazepine concentration in group I was (7.37±3.67)mcg/ml and in group III (5.65±2.37) mcg /ml (p=0.09). Mean serum phenytoin in group II was (15.16±6.48) mcg /ml and in group III (12.66±5.5) mcg/ml (p=0.2). When used singly carbamazepine showed 30% subtherapeutic and 20 % toxic concentrations. Whereas in combination group the plasma concentrations of carbamazepine were found to be therapeutic, subtherapeutic and toxic ranges in 55%, 40% and 5% patients, respectively. In phenytoin monotherapy group the concentrations were subtherapeutic in 15%, therapeutic in 65% and in toxic range in 20% patients, whilst in combination group the concentrations obtained were 50%, 40 and 10% respectively.
Conclusion: Co-administration of carbamazepine and phenytoin do not affect the serum concentrations of either group significantly. It’s possible that Indian population has different therapeutic range of antiepileptic drugs from that given in standard literature. But larger study needs to be done to confirm the results.
Keywords: Therapeutic drug monitoring, HPLC, Phenytoin, Carbamazepine.
References
1. 1. Santhosh NS, Sinha S, Satishchandra P. Epilepsy : Indian perspective. 2014;17(March).
2. Reaction AD. Phenytoin and carbamazepine cross reactivity: report of a case and review of literature. 2003;703–4.
3. Lowenstein D. H. Seizures and EpilepsyFauci A.S, Braunwald E, Kasper D. L, Hauser S. L, Longo D. L, Jameson J. L, Loscalzo J. Harrison's Principles of Medicine. 17th edition.2008.
4. Brunton L. L, Chabner B. A, Knollmann B. C. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th Ed. Chapter 21;Pharmacotherapy of the Epilepsies, page 526-582
5. Trost LF, Wender RC, Suter CC, Von Worley AM, Brixner DI, Rosenberg JH, Gunter MJ."Management of epilepsy in adults. Treatment guidelines". Postgraduate Medicine, December 2005, 118 (6): 29–33
6. C.L. Deckers, S.J. Czuczwar, Y.A. Hekster, A. Keyser, H. Kubova, H. Meinardi, et al.,Selection of antiepileptic drug polytherapy based on mechanisms of action: theevidence reviewed, Epilepsia 41 (2000) 1364–1374.
7. F. Bugamelli, C. Sabbioni, R. Mandrioli, E. Kenndler, F. Albani, M. Raggi, Simulta-neous analysis of six antiepileptic drugs and two selected metabolites in humanplasma by liquid chromatography after solid-phase extraction, Anal. Chim. Acta472 (2002) 1–10.
8. L. Budakova, H. Brozmanova, M. Grundmann, J. Fischer, Simultaneous determi-nation of antiepileptic drugs and their two active metabolites by HPLC, J. Sep.Sci. 31 (2008) 1–8.
9. K.M. Patil, S.L. Bodhankar, Simultaneous determination of lamotrigine,phenobarbitone, carbamazepine and phenytoin in human serum by high-performance liquid chromatography, J. Pharm. Biomed. Anal. 39 (2005)181–186.
10. H.M. Neels, A.C. Sierens, K. Naelaerts, S.L. Scharpé, G.M. Hatfield, W.E. Lambert, Therapeutic drug monitoring of old and newer anti-epileptic drugs, Clin. Chem.Lab. Med. 42 (2004) 1228–1255.
11. P.N. Patsalos, W. Fröscher, F. Pisani, C.M. van Rijn, The importance of druginteractions in epilepsy therapy, Epilepsia 43 (2002) 365–385.
12. G.A. Khoschsorur, F. Frühwirth, G. Halwachs-Baumann, Simple and rapid HPLCmethod for simultaneous determination of multiple antiepileptic drugs inhuman serum, Chromatographia 54 (2001) 345–349.
13. Ferreira A, Rodrigues M, Oliveira P, Francisco J, Fortuna A, Rosado L, et al. Liquid chromatographic assay based on microextraction by packed sorbent for therapeutic drug monitoring of carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin and the active metabolites carbamazepine-10,11-epoxide and licarbazepine. J Chromatogr B Anal Technol Biomed Life Sci [Internet]. 2014;971:20–9. Available from: http://dx.doi.org/10.1016/j.jchromb.2014.09.010
14. Johannessen SI, Strandjord RE. The influence of phenobarbital and phenytoin on carbamazepine serum level. In: Schneider H, Janz D, Gardner-Thorpe C, Meinardi H, Sherwin AL, eds. Clinical pharmacology of anti-epileptic drug. Berlin: Springer-Verlag, 1975:201-5
15. Wang RD, Liu LT, Yiu CH, Chang TY. Carbamazepine drug interactions: the influence of concurrent drug therapy on serum concentrations of carbamazepine and its epoxide metabolite.Chin Med J (Taipei) 1990;45:222-32.
16. Liu H, Delgado MR, Browne RH. Interactions of valproic acid with carbamazepine and its metabolites’ concentrations, concentrations ratios, and level/dose ratios in epileptic children. Clin Neuropharmacol [Internet]. 1995;18(1):1–12. Available from: http://www.ncbi.nlm.nih.gov/pubmed/866552
17. Chapron DJ, LaPierre BA, Abou-Elkair M. Unmasking the significant enzyme-inducing effects of phenytoin on serum carbamazepine concentrations during phenytoin withdrawal. Ann Pharmacother 1993;27:708-11.
DOI: https://dx.doi.org/10.18535/jmscr/v5i5.230
