The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine

Heiningen, P. N. M. Van; Eve, Malcolm D.; Oosterhuis, B.; Jonkman, J. H. G.; Bruin, H. De; Hulsman, J.A.R.J.; Richens, A.; Jensen, Pia Søe

doi:10.1038/clpt.1991.158

Cited by 77 publications

(27 citation statements)

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“…The faster apparent clearance in women in comparison to men may compensate, at least partially, the lower body weight effect on the pharmacokinetic parameters, resulting in relatively similar values in both genders. No pharmacokinetic gender-related differences were observed with oxcarbazepine, a compound chemically related to eslicarbazepine acetate [15].…”

Section: Discussionmentioning

confidence: 97%

Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2‐093), a new voltage‐gated sodium channel blocker

Falcão

Maia

Almeida

et al. 2007

Biopharm & Drug Disp

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Purpose. To determine the effect of gender on the pharmacokinetics of eslicarbazepine acetate, a novel voltage-gated sodium channel blocker in the development for the treatment of epilepsy and bipolar disorder.Methods. Single-centre, open-label, parallel-group study in 12 female and 12 male healthy subjects. The study consisted of a single-dose (600 mg) period and a multiple-dose (600 mg, oncedaily, for 8 days) period, separated by 4 days.Results. Eslicarbazepine acetate was rapidly and extensively metabolized to eslicarbazepine (S-licarbazepine), the main active metabolite. Following a single-dose, arithmetic mean eslicarbazepine maximum plasma concentrations (C max ) and area under the plasma concentration-time curve over 24 h (AUC 0À24 ) and from 0 to infinity (AUC 0À1 ) were, respectively, 9.3 mg/ml, 128.5 mg h/ml and 171.9 mg h/ml in male subjects and 10.1 mg/ml, 150.1 mg h/ml and 205.0 mg h/ml in female subjects. At steady-state, C max , AUC 0À24 and AUC 0À1 were 15.5 mg/ml, 207.8 mg h/ml and 295.8 mg h/ml in male subjects, and 16.8 mg/ml, 214.5 mg h/ml and 295.2 mg h/ml in female subjects. Steady-state plasma concentrations were attained at 4 to 5 days of administration in both groups.Eslicarbazepine C max , AUC 0À24 and AUC 0À1 female:male geometric mean ratios (90%CI) were, respectively, 1.09 (0

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Section: Discussionmentioning

confidence: 97%

Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2‐093), a new voltage‐gated sodium channel blocker

Falcão

Maia

Almeida

et al. 2007

Biopharm & Drug Disp

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“…10-OHcarbamazepine is then metabolized further by glucuronidation and excreted by the kidneys. The most extensive elderly oxcarbazepine study involved low doses of oxcarbazepine given to 12 young and 12 elderly healthy males, and 12 young and 12 elderly female volunteers (27). At low doses of oxcarbazepine (300-600 mg/day) a significantly higher maximum concentration, higher area under the curve parameters, and a lower elimination rate constant was observed in the elderly volunteers.…”

Section: Oxcarbazepinementioning

confidence: 99%

Epilepsy in the Elderly

Leppik

2006

Epilepsia

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Summary: The elderly are the most rapidly growing segment of the population and the incidence of epilepsy is higher in the elderly than in any other age group. They have been subdivided into the “young old,” 65–74 years, “middle old” 75–84 years, and the “old old,” 85 years or older. But further subdivisions are needed: persons with only epilepsy, those with epilepsy and multiple medical problems, and the frail elderly. Thus, when considering therapy, one must tailor the interventions to nine categories: young old healthy, young old with medical problems, frail young old, old healthy, old with medical problems, frail old, old old healthy, old old with medical problems, and frail old old. The prevalence of antiepileptic drug (AED) use in community dwelling elderly is 1.5%; in the nursing home population it is 10%. Surprisingly, 3% have an AED newly prescribed after admission. Overall, 6.2% were using phenytoin, 1.8% carbamazepine, 0.9% valproic acid, 1.7% phenobarbital, and others combined, 1.2%. AEDs rank fifth among all drug categories as a cause of adverse reactions. There are very few data regarding the clinical use of AEDs in the elderly. The paucity of information makes it very difficult to recommend specific AEDs with any confidence that the outcomes will be optimal. An appropriate for elderly healthy may not be appropriate for elderly with multiple medical problems, and in frail elderly variable absorption may be a major problem. One of the major advantages of some newer AEDs is lack of drug interactions. Cost is an advantage of the older AEDs. Regardless of the AED chosen, one must use doses appropriate to the clearance of the drug, and AED levels, especially unbound (free) levels, must be monitored. The elderly nursing home resident may be more frail, be taking many medications, and have several concomitant illnesses, making them difficult to treat. The most commonly used AED, phenytoin, may not be the easiest or safest AED to prescribe in the elderly with multiple medical problems or the frail elderly.

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“…Some decrease in drug clearance in elderly patients has also been documented with lamotrigine (31) and monohydroxycarbazepine (32). For tiagabine, no pharmacokinetic alterations have been recorded in old age except for a moderate increase in area under the time-concentration curve after multiple dosing (33).…”

Section: The Elderlymentioning

confidence: 99%

The Clinical Pharmacokinetics of the New Antiepileptic Drugs

Perucca

1999

Epilepsia

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Summary: Because pharmacokinetics is a major determinant of the magnitude and duration of pharmacologic response, understanding the kinetic properties of the new antiepileptic drugs (AEDs) is essential for the correct use of these compounds in clinical practice. After oral administration, absorption is rapid and relatively efficient for the new AEDs, the most notable exception being gabapentin, whose bioavailability decreases with increasing dosage. None of the new AEDs is extensively bound to plasma proteins except for tiagabine, which is over 95% protein-bound. The route of elimination differs to an important extent from one compound to another, and elimination half-lives range from over 30 h for zonisamide to 5-7 h for gabapentin. For all drugs that are metabolized, half-life is shortened and clearance is increased when patients receive concomitant enzyme-inducing agents such as barbiturates, phenytoin, and carbamazepine. Lamotrigine metabolism is markedly inhibited by valproic acid, and felbamate may increase the serum levels of most other AEDs. Felbamate, topiramate, and oxcarbazepine may also reduce the efficacy of the contraceptive pill by stimulating its metabolism. Key Words: AntiepilepticsPharmacokinetics-Drug interactions.To exert their therapeutic effects, antiepileptic drugs CLINICAL PHARMACOKINETICS (AEDs) must be absorbed and reach their sites of action in the brain at concentrations sufficient to produce the desired pharmacologic response. The pharmacokinetic profile is a major determinant of the magnitude and duration of drug action and is one of the factors to be considered in determining the optimal number of daily doses and the minimal interval that should elapse between dosage adjustments. For any given drug, pharmacokinetics may vary markedly from one patient to another (in relation to genetic background, age, physiologic states such as pregnancy, associated disease, and concomitant treatments), resulting in altered dosage requirements. Therefore, full understanding of the pharmacokinetic properties of individual compounds, and the factors affecting them, is essential for correct use of AEDs in clinical practice. Over the past decade, several new AEDs (felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin, and zonisamide) have been introduced into routine clinical practice in a number of counThe pharmacokinetics of the new AEDs have been evaluated in healthy volunteers and in patients with epilepsy receiving a variety of concomitant treatments. For vigabatrin and for monohydroxycarbazepine (the active metabolite of oxcarbazepine), evaluation of pharmacokinetic properties is complicated by the presence of an asymmetric carbon in the molecule, which determines the existence of two different stereoisomers. Although vigabatrin is administered as a racemic mixture of the (R)-and (S)-isomers, only the (S)-form is pharmacologically active, and pharmacokinetic data for vigabatrin quoted in' this review refer to the (S)-enantiomer. In the case of monohydroxycarbazepine...

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The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine

Cited by 77 publications

References 3 publications

Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2‐093), a new voltage‐gated sodium channel blocker

Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2‐093), a new voltage‐gated sodium channel blocker

Epilepsy in the Elderly

The Clinical Pharmacokinetics of the New Antiepileptic Drugs

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