The influence of food on the disposition of the antiepileptic oxcarbazepine and its major metabolites in healthy volunteers

Degen, P.H.; Flesch, G.; Cardot, J; Czendlik, C.; Dieterle, W.

doi:10.1002/bdd.2510150609

Cited by 28 publications

(11 citation statements)

References 7 publications

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“…It had been reported that the systemic bioavailability of MHD was increased by approximately 17% when oxcarbazepine was taken with food. 59,60 However, with a newer oxcarbazepine formulation, there was no effect of food on the bioavailability of MHD (data on file, Novartis Pharmaceuticals Corp.). Peak plasma concentrations of MHD occurred 4-6 hours after a single dose of either oxcarbazepine 400 mg or oxcarbazepine 600 mg. 57,61 The plasma terminal half-life of oxcarbazepine was between 1 and 2.5 hours, 62 whereas the plasma MHD terminal halflife averaged 9.3 ± 1.8 hours after administration of a single dose.…”

Section: Clinical Pharmacokineticsmentioning

confidence: 99%

Oxcarbazepine in the Treatment of Epilepsy

Glauser¹

2001

Pharmacotherapy

247

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Oxcarbazepine is a new antiepileptic drug (AED) that has been registered in more than 50 countries worldwide since 1990 and recently received approval in the United States and the European Union. Oxcarbazepine is a keto analog of carbamazepine and has a more favorable pharmacokinetic profile. It is rapidly absorbed after oral administration and undergoes rapid and almost complete reductive metabolism to form the pharmacologically active 10-monohydroxy derivative. Oxcarbazepine exhibits linear pharmacokinetics, no autoinduction, and minimal interaction with other AEDs. Ten controlled trials demonstrated that oxcarbazepine is safe and efficacious in the treatment of partial seizures across a wide range of ages (children to adults), situations (recent onset to treatment-resistant epilepsy), and uses (monotherapy and adjunctive therapy). The most common treatment-emergent adverse events are related to the central nervous system. Treatment-emergent hyponatremia (defined as serum sodium level < 125 mEq/L) occurred in 3% of patients treated with oxcarbazepine in clinical trials. According to the efficacy and safety profile established in the controlled trials, oxcarbazepine represents an important new treatment option indicated for monotherapy and adjunctive therapy in adults with partial seizures and as adjunctive therapy in children aged 4 years or older with partial seizures. Although structurally similar to carbamazepine, significant differences exist in the pharmacokinetics, drug interaction potential, adverse-effect profile, and dosage and titration between these two agents, and they should be considered distinct therapeutic agents.

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Section: Clinical Pharmacokineticsmentioning

confidence: 99%

Oxcarbazepine in the Treatment of Epilepsy

Glauser¹

2001

Pharmacotherapy

247

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“…The 2 formulations manifested equivalent therapeutic efficacy.b) 10 healthy volunteers,b) Chronopharmacokinetics of PHT2. No evidence that circadian rhythms influenced absorption and distribution.Degen et al, 1994 [112]6 healthy volunteersEffect of food on pharmacokinetics of OXC1. AUC: increased by 16 % and Cmax increased by 23 % when OXC was given with food.2.…”

Section: Chronopharmacodynamics Of Epilepsy Medicationsmentioning

confidence: 99%

Chronopharmacology of Anti-Convulsive Therapy

Ramgopal

Thomé‐Souza

Loddenkemper

2013

Curr Neurol Neurosci Rep

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Approximately one-third of patients with epilepsy continue to have seizures despite antiepileptic therapy. Many seizures occur in diurnal, sleep/wake, circadian, or even monthly patterns. The relationship between biomarkers and state changes is still being investigated, but early results suggest that some of these patterns may be related to endogenous circadian patterns whereas others may be related to wakefulness and sleep or both. Chronotherapy, the application of treatment at times of greatest seizure susceptibility, is a technique that may optimize seizure control in selected patients. It may be used in the form of differential dosing, as preparations designed to deliver sustained or pulsatile drug delivery or in the form of ‘zeitgebers’ that shift endogenous rhythms. Early trials in epilepsy suggest that chronopharmacology may provide improved seizure control compared with conventional treatment in some patients. The present article reviews chronopharmacology in the treatment of epilepsy as well as future treatment avenues.

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“…41, Suppl. 8,2000 a complex combination of drug interactions may lead to serious adverse events. It is possible that other such interactions occur that have not yet been elucidated.…”

Section: Hepatic Inductionmentioning

confidence: 99%

Antiepileptic Drug Interactions

French

Gidal

2000

Epilepsia

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Summary: This article reviews the potential interactions of antiepileplic drugs (AEDs) and the pharrnacokinetic and pharmacodynamic principles involved. It describes the absorptive and distributive properties of AEDs and the effects on protein binding, hcpatic metabolism, and elimination resulting from co-administration of AEDs with food or other drugs. Drug behavior is a function of absorption, metabolism, distribution, and elimination. Administration or either multiple AEDs or a combination of AEDs plus drugs for other conditions can modify any of these physiologic processes, possibly rcsulting in complex interactions. These may include alterations in the bioavailability and absorption of a drug and changes in half-life and serum level through induction or inhibition of hepatic metabolism. In most cases, increases or decreases in serum concentrations will signal a drug interaction. In other cases, clinically significant drug interactions remain undetected owing to apparently stable serum concentrations. Co-administration of drugs may affect the rate of clearance of one or both drugs. The erfect on clearance varies, owing to gcnctic factors, patient characteristics (age and presence of co-morbidities), and individual responses. AEDs that induce hepatic metabolism can also influence the metabolism of concomitantly administered non-epilepsy medications and can interfere with oral contraceptives, as well as vitamins D and K. Patients with renal insufficiency or advanced age may experience incomplete renal excretion and should receive reduced dosages of drug. Undcrstanding the pharrnacokinetics and pharmacodynamic properties of AEDs and the route of metabolism of all competing drugs is important for optimal management of patients with epilepsy and for prevention of avoidable drug interactions. Key Words: Antiepileptic drug-Drug interaction-DistributionElimination-Inhibition Antiepileptic drugs (AEDs) have the most complex pharmacokinetic properties of any class of drug. When a drug enters the body, its activity is governed by the route and speed of absorption, metabolism, distribution, and elimination. Concomitant administration with another drug can precipitate complex interactions in response to any one of these physiologic processes. Serum concentrations of co-administered drugs may be increased or decreased, possibly resulting in clinical toxicity or diminished therapeutic effect. In the absence of pharmacokinetic interactions, pharmacodynamic interactions may occur, modifying side effects or pharmacologic effects without changing drug serum concentrations. These interactions may manifest as minor inconveniences or, in some cases, as serious and potentially harmful effects.Understanding the pharmacokinetics, pharmacodynamics, and their basic mechanisms is critical to the optimal use of AEDs. A variety of factors specific either to the drug or to the patient can affect the length and magnitude of a pharmacokinetic interaction. These properties Address correspondence and reprint requests to Dr.

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The influence of food on the disposition of the antiepileptic oxcarbazepine and its major metabolites in healthy volunteers

Cited by 28 publications

References 7 publications

Oxcarbazepine in the Treatment of Epilepsy

Oxcarbazepine in the Treatment of Epilepsy

Chronopharmacology of Anti-Convulsive Therapy

Antiepileptic Drug Interactions

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