title: The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist.
abstract: The clinical pharmacology profile of a drug critically determines its therapeutics, and this review summarizes the characteristics associated with the antiepileptic drug (AED) perampanel. A PubMed literature search was performed for perampanel. Congress abstract data are included where necessary and Eisai Ltd provided access to unpublished data on file. After oral ingestion, perampanel is rapidly absorbed and peak plasma concentrations occur 0.5-2.5 h later; its bioavailability is ~100%. Although the rate of perampanel absorption is slowed by food co-ingestion, the extent absorbed remains unchanged; therefore, perampanel can be administered without regard to meal times. The pharmacokinetics of perampanel are linear and predictable over the clinically relevant dose range (2-12 mg); perampanel is 95% protein-bound to albumin and α1-acid glycoprotein. Perampanel is extensively metabolized (>90%) in the liver, primarily by cytochrome P450 (CYP) 3A4, to various pharmacologically inactive metabolites. In healthy volunteers, the apparent terminal half-life is ~105 h, whereas the calculated effective half-life is 48 h. These half-life values allow for once-daily dosing, which will aid patient compliance and in the event of a missed dose, will have minimal impact on seizure control. In healthy volunteers prescribed carbamazepine, half-life decreases to 25 h. Clearance values are not significantly different in adolescents (~13.0 ml/min) and the elderly (~10.5 ml/min) compared with adults (10.9 ml/min). Perampanel has minimal propensity to cause pharmacokinetic interactions. However, it is the target of such interactions and CYP3A4-inducing AEDs enhance its clearance; this can be used to advantage because dose titration can be faster and thus optimum therapeutic outcome can be achieved sooner. Perampanel 12 mg, but not 4 or 8 mg, enhances the metabolism of the progesterone component of the oral contraceptive pill, necessitating the need for an additional reliable contraceptive method. Overall, perampanel has a favorable clinical pharmacology profile, which should aid its clinical use.
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL-Institute of Neurology, Queen Square, London, United Kingdom; Epilepsy Society, Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Patsalos
mesh_terms: D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D009570:Nitriles; D011485:Protein Binding; D011728:Pyridones / Q000494:pharmacology* / Q000627:therapeutic use; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; D018091:Receptors, AMPA; C551441:perampanel
keywords: Clinical pharmacology; Drug-drug interactions; Pharmacodynamics; Pharmacokinetics; Plasma protein binding