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  • 1
    ISSN: 1432-2072
    Keywords: Epilepsy ; Anticonvulsants ; Viloxazine ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to evaluate the influence of chronic antiepileptic drug treatment on the kinetics of the antidepressant viloxazine (VLX), six drug-free control subjects and six epileptic patients treated with one or two anticonvulsants (phenobarbital, carbamazepine or phenytoin) were given a single oral dose of VLX (200 mg). On a separate occasion, the patients were also given 200 mg VLX by IV infusion. Plasma VLX levels were determined by GLC. Following oral dosing, VLX was rapidly absorbed from the gastrointestinal tract (peak levels at 0.5–4 h); plasma level profiles showed a considerable interindividual variability but did not differ significantly between patients and controls. Terminal half-lives were 4.3±1.5 h in the patients and 4.3±1.8 h in the controls. Clearance and volume of distribution calculated after IV dosing in the patients were 124±11 ml h−1 kg−1 and 0.73±0.28 l/kg, respectively. The absolute oral availability was 85±14%. At variance with findings reported for other antidepressants, VLX kinetics do not appear to be significantly altered by concurrent treatment with enzyme-inducing antiepileptic drugs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1590-3478
    Keywords: Epidemiology ; Clinical ; Impact ; Antiepiletic drug interation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario Il presente studio è stato condotto al fine di valutare, in condizioni cliniche rutinarie, i possibili effetti delle interazioni farmacocinetiche degli anticonvulsivanti su: (I) le prescrizioni delle dosi giornaliere e (II) la variabilità dei livelli plasmatici dei singoli farmaci. La casistica comprende 848 pazienti epilettici sottoposti, per la prima volta ad un dosaggio ematico e trattati cronicamente con uno o due dei seguenti farmaci: fenitoina (PHT), fenobarbital (PB), carbamazepina (CBZ) e valproato (VPA). Nessuna differenza significativa è stata osservata nelle prescrizioni delle dosi giornaliere tra i gruppi in monoterapia e quelli in biterapia. Per quanto riguarda la variabilità dei livelli ematici, sono state osservate le seguenti differenze statisticamente significative: (I) una più alta percentuale di pazienti con livelli di CBE e VPA al di sotto dei «ranges» tereapeutici nei gruppi che assumevano tali farmaci in associazione con uno degli altri considerati, rispetto ai gruppi in monoterapia; (II) una percentuale più alta di pazienti con livelli di PB al di sopra del «range» nel gruppo trattato con PB e PHT in associazione, rispetto agli altri gruppi considerati. Le implicazioni cliniche di tali dati vengono, quindi, discusse.
    Notes: Abstract The impact of pharmacokinetic anticonvulsant drug interactions on prescribing patterns and serum drug level distribution in a routine clinical setting was evaluated in a population of 848 patients chronically treated with phenytoin, phenobarbital, carbamazepine and valproic acid (either alone or as two-drug combinations) and referred for therapeutic drug monitoring for the first time. While dosages of each drug did not differ significantly between monotherapy and polytherapy patients, significant differences in serum level distribution were found. The proportion of patients with suboptimal serum carbamazepine and valproic acid levels (〈4 and 〈50μg/ml, respectively) was much greater in the polytherapy than in the monotherapy groups, probably as a consequence of induction of carbamazepine and valproic acid metabolism by combined anticonvulsants. Conversely, the proportion of phenobarbital levels above the upper limit of the optimal range (40μg/ml) was greater among patients receiving phenytoin in combination than among patients taking phenobarbital alone, presumably as a result of phenytoin-induced inhibition of barbiturate metabolism. The therapeutic implications of these findings are discussed.
    Type of Medium: Electronic Resource
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