Antiepileptic drugs pharmacokinetics

Factors Affecting Antiepileptic Drug Pharmacokinetics in Community-Dwelling Elderly James C. Cloyd, Susan Marino, and Angela K. Bimbaum... 

The antiepileptic drug phenytoin, an orally available class DB antiarrhythmic, is mainly effective in digitalis-induced arrhythmias. This diug exhibits nonlinear pharmacokinetics and a number of side effects including neuropathy, gingival hypetplasia, hepatitis, immunological disorders and suppression of white blood cells. 

Many authors reported poor elimination of antiepileptic drug carbamazepine [6,13,17,49, 54]. Pharmacokinetic data indicate that only 1-2% of carbamazepine is excreted unmetabolized. However, glucuronide conjugates of carbamazepine can presumably be cleaved in the sewage, and thus increase its environmental concentrations [51]. This is confirmed by its high ubiquity in the enviromnent at concentration levels of several hundred nanograms per liter in different surface waters. Due to its recalcitrant nature, it can be used as anthropogeiuc marker for the contamination of aquatic environment. 

Data from Fought Pharmacokinetic considerations in prescribing antiepileptic drugs. Epilepsia 2001 42(Suppl 4) 19-23 Leppik IE. Contemporary Diagnosis and Management of the Patient with Epilepsy, 6th ed. Newton, PA Handbooks in Health Care, 2006.02-149 and Bourgeois BED. Pharmacokinetics and pharmacodynamics of antiepiieptic drugs. In WyllieE. ed. The Treatment of Epilepsy, 4th ed. Philadelphia Lippincott Williams 8 Wilkins, 2006 656-669. 

Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age. Clin Pharmacokinet 2006 45(4) 351-63. 

Cloyd, J.C., Fischer, J.H., Kriel, R.L., and Kraus, D.M. (1993) Valproic acid pharmacokinetics in children. IV. Effects of age and antiepileptic drugs on protein binding and intrinsic clearance. Clin Pharmacol Ther 53 22-29. 

Ram beck, B., Specht, U., and Wolf, P. (1996) Pharmacokinetic interactions of the new antiepileptic drugs. Clin Pharmacokinet 31 309-324. 

McAuley JW, Anderson GD Treatment of epilepsy in women of reproductive age Pharmacokinetic considerations. Clin Pharmacokinet 2002 41 559. Meldrum BS, Rogawski MA Molecular targets for antiepileptic drug development. Neurotherapeutics 2007 4 18. [PMID 17199015]... 

Pharmacokinetic considerations when prescribing antiepileptic drugs... 

Antiepileptic Drug Therapy in Pregnancy I Gestation-Induced Effects on AED Pharmacokinetics... 

Pharmacodynamic and Pharmacokinetic Interactions of Psychotropic Drugs with Antiepileptic Drugs... 

Mahmood I, Balian JD. Interspecies scaling Predicting pharmacokinetic parameters of antiepileptic drugs in humans form animals with special emphasis on clearance. J Pharm Sci 1996 85 411-4. 

Lanchote VL, Garcia FS, Dreossi SA, Takayanagui OM. Pharmacokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neuro-cysticercosis. Ther Drug Monit 2002 24(3) 338 5. 

The effects of other antiepileptic drugs on the pharmacokinetics of lamotrigine have been studied in 62 patients with epilepsy (71). Carbamazepine, phenytoin, and phenobarbital, all enzjme inducers, increased the oral clearance of lamotrigine, individually by 58% and in combination by nearly 200%. 

Besag FM, Berry DJ, Pool F. Methsuximide lowers lamotrigine blood levels a pharmacokinetic antiepileptic drug interaction. Epilepsia 2000 41(5) 624-7. 

Perucca E, Bialer M. The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine. Clin Pharmacokinet 1996 31(1) 29 6. 

Very few examples of outcomes research in neurological pharmacy exist. However, one historical control study determined that the implementation of a pharmacokinetics consultation service in an epilepsy clinic decreased seizure frequency and number of adverse effects compared with the baseline frequency in the 4 months prior to offering the service.A second study conducted in the pediatric epilepsy population described the effect of establishment of a specialty pediatric epilepsy clinic with clinical pharmacy services. Compared with patients seen before the beginning of the clinic, patients seen in the specialty clinic had decreased numbers of antiepileptic drugs and decreased doses of these medications. Frequency of seizures was not examined in this report. 

The appropriate use of antiepileptic drugs requires a thorough understanding of their clinical pharmacology, e.g., mechanism of action, pharmacokinetics, adverse reaction, dosage forms, and drug interactions. 

Shah J, Shellenberger K, Canafax DM. Zonisamide Chemistry, biotransformation, and pharmacokinetics. In Levy RH, Mattson RH, Meldrum BS, et al, ed. Antiepileptic Drugs, 5th ed. Philadelphia, Lippincott Williams Wilkins, 2002 873-879. 

ConMeds can also be classified into groups by either therapeutic area or by mechanism of interaction. For example, many antiepileptic drugs are known to be metabolic inducers. One could then classify whether the ConMed was an antiepileptic or not and use this as a covariate in an analysis. Using such an approach, Yukawa et al. (2002) classified ConMeds into 0 if the ConMed was phenobarbital, phenytoin, or carbamaze-pine or T if none of the above. PopPK analysis of 218 Japanese subjects revealed that these three ConMeds increased haloperidol clearance by 32%. Of course, this approach assumes that these three inducers all have the same time course and effect on the pharmacokinetic parameter that they affect, which may not be the case. 

Browne, TR. Pharmacokinetics of antiepileptic drugs. Neurology 1998 51(Suppl 4) S2-S7. 

Gidal BE, Baltes E, Otoul C, et al. Effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs a pooled analysis of data from randomized clinical trials. Epilepsy Res 2005 64 1-11. 

Morselli, P. L. and Fracno-MorseUi, R., Clinical pharmacokinetics of antiepileptic drugs in adults. Pharmacol. Ther., 10 65-101, 1980. 

Sherwin, A. L., Ethosuximide Chnical use, m Antiepileptic Drugs, 4th ed.. Levy, R. H., Mattson, R. H., and Meldrum, B. S., Eds., Raven Press, New York, 1994. Battino, D., Estienne, M., and Avanzini, G., Chnical pharmacokinetics of antiepileptic drugs in paediatric patients. Part 1 Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide, Clin. Pharmacokinet., 29 257-286, 1995. 

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