Levetiracetam pharmacokinetics

Perucca E, Gidal BE. Effects of anti epileptic comedication on levetiracetam pharmacokinetics A pooled analysis of data, from randomized adjunctive therapy trials. Epilepsy Res 2003 53 47-56. 

Pharmacokinetics Absorption is rapid, with peak plasma concentrations occurring in approximately 1 hour following oral administration in fasted subjects. Steady state is achieved after 2 days of multiple twice/day dosing. Levetiracetam is not extensively metabolized. The plasma half-life in adults is approximately 7 hours. Levetiracetam is eliminated from the systemic circulation by renal excretion. 

Because levetiracetam is not metabolized by CYP450 enzymes and does not inhibit or induce CYP450 enzymes, it is unlikely to have significant pharmacokinetic drug interactions... 

In 11 healthy adults in a double-blind, placebo-controlled study levetiracetam had no effect on the steady-state pharmacokinetics of digoxin or the actions of digoxin on the electrocardiogram (264). 

In a double-blind, crossover stndy 18 healthy women taking an oral contraceptive containing ethinylestradiol 30 xg plus levonorgestrel 150 pg took levetiracetam 500 mg/day or placebo (20). The plasma concentrationtime curves and pharmacokinetics of ethinylestradiol and levonorgestrel were not altered. 

Levy RH, Ragueneau-Majlessi I, Baltes E. Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Epilepsy Res 2001 46(2) 93-9. 

Ragueneau-Majlessi I, Levy RH, Janik F. Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Epilepsia 2002 43(7) 697-702. 

Ragueneau-Majlessi I, Levy RH, Meyerhoff C. Lack of effect of repeated administration of levetiracetam on the pharmacodynamic and pharmacokinetic profiles of warfarin. Epilepsy Res 2001 47(l-2) 55-63. 

Drug Interactions. Levetiracetam neither inhibits nor indnces the CYP450, UGT, or epoxide hydrolase enzyme systems, and in vitro data predict a low potential for pharmacokinetic interactions. Levetiracetam does not appear to interact with other AEDs, warfarin, digoxin, or oral contraceptive drngs. ° ... 

The risk of clinically relevant drug interactions is minimal with S-(-)-levetiracetam, because it does not alter the pharmacokinetics of coadministered drugs by inhibition or induction of hepatic enzymes (84). Toxic effects include mild to moderate somnolence, asthenia, ataxia, and dizziness these effects seldom require discontinuance. An increase in the incidence of behavioral abnormalities in children and in adults having a previous history of neuropsychiatric problems has been noted (85). Its use in the elderly or in patients with renal Impairment will require an individualization of dose, and an additional dose is needed after renal dialysis. Levetiracetam was associated with developmental toxicity in the offspring of pregnant animals. 

Patsalos PN. Pharmacokinetic profile of levetiracetam toward ideal characteristics. Pharmacol Ther 2000 85 77-85. 

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. 

In a controlled study, levetiracetam did not alter the pharmacokinetics or pharmacodynamics of warfarin. 

There is some evidence that the enzyme-inducing antiepileptics (carbamazepine, phenobarbital, phenytoin and primidone) may modestly reduce levetiracetam levels, but this is not thought to be clinically relevant. Levetiracetam does not usually alter the levels of these antiepileptics. However, some studies have found modestly raised phenytoin levels, and cases of possible carbamazepine toxicity have also been reported. There appears to be no pharmacokinetic interaction between levetiracetam and gabapentin, lamotrigine, or valproate. 

Giuliano Hiersemenzel R, Baltes E, Johnscher G, Janik F, Weber W. Influence of a new antiepileptic drug (Levetiracetam, ucb L059) on the pharmacokinetics and plarmacodynamics of oral contraceptives. Epilepsia (1996) 37,90. 

Uges JW, van Huizen MD, Engelsman J, Wilms EB, Touw DJ, Peelers E, Vecht CJ. Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus. Epilepsia 2009 50(3) 415-21. 

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