The effects of phenytoin on phenobarbitone and primidone metabolism.

Lambie, David G.; Johnson, Ralph H.

doi:10.1136/jnnp.44.2.148

Cited by 19 publications

(2 citation statements)

References 8 publications

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“…In particular, concurrent administration of PHT was associated with a modest decrease in PB CL/F, which reached statistical significance within the elderly group. A decrease in PB CL/F by PHT is consistent with results of previous studies, in which PHT was found to increase serum PB concentration, presumably by inhibiting PB metabolism (23,24). In our study, CBZ also appeared to have a modest lowering effect on PB CL/F, although again this reached statistical significance only in the elderly population.…”

Section: Discussionsupporting

confidence: 92%

Phenobarbital Pharmacokinetics in Old Age: A Case‐matched Evaluation Based on Therapeutic Drug Monitoring Data

et al. 2005

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Summary:Purpose: To assess the influence of aging on the pharmacokinetics of phenobarbital (PB) at steady state in patients receiving long-term therapy.Methods: Serum PB concentrations from the database of the therapeutic drug monitoring service of a large neurological hospital were used to calculate apparent clearance values (CL/F) in 224 patients aged 65 years and older (mean, 73 ± 6.1 years). CL/F values in these patients were compared with those determined in an equal number of controls aged 20 to 50 years (mean, 35.7 ± 7.9 years) and matched for gender, body weight, and type of anticonvulsant comedication. Correlations of CL/F with age, body weight, gender, and comedication also were explored within each age group.Results: PB CL/F values were significantly lower in elderly patients than in controls (3.2 ± 0.8 vs. 4.1 ± 1.2 ml/h/kg; p < 0.0001). Age was identified as a statistically significant predictor of CL/F at multiple regression analysis, but it accounted for only a modest component of the interindividual pharmacokinetic variation. Comedication with carbamazepine (CBZ) and phenytoin (PHT) was associated with a moderate decrease in PB CL/F, which reached statistical significance in the elderly group (p < 0.01 for CBZ comedication; p < 0.001 for PHT comedication).Conclusions: Aging is associated with a significant decrease in PB clearance, which might be related to a reduction in glomerular filtration rate or diminished drug-metabolizing capacity in the liver or both. Because of this, older patients will require lower dosages to achieve serum PB concentrations comparable with those found in nonelderly adults.

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Section: Discussionsupporting

confidence: 92%

Phenobarbital Pharmacokinetics in Old Age: A Case‐matched Evaluation Based on Therapeutic Drug Monitoring Data

et al. 2005

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“…Phenobarbital concentrations have been reported to increase upon introduction of phenytoin comedication (Lambie & Johnson 1981;Morselli et a1. 1971).…”

Section: Phenytoinmentioning

confidence: 99%

Antiepileptic Drugs

Patsalos

Duncan

1993

Drug Safety

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Approximately 20 to 30% of patients with active intractable epilepsy are commonly treated with polytherapy antiepileptic drug regimens, and these patients may experience complicated drug interactions. Furthermore, because of the long term nature of treatment, the possibility of drug interactions with drugs used for the treatment of concomitant disease is high. Classically, clinically significant drug interactions, both pharmacokinetic and pharmacodynamic, have been considered to be detrimental to the patient, necessitating dosage adjustment. However, this need not always be the case. With the introduction of new drugs (e.g. vigabatrin and lamotrigine) with known mechanisms of action, the possibility exists that these can be used synergistically. The most commonly observed clinically significant pharmacokinetic interactions can be attributed to interactions at the metabolic and serum protein binding levels. The best known examples relate to induction (e.g. phenobarbital, phenytoin, carbamazepine and primidone) or inhibition [e.g. valproic acid (sodium valproate)] of hepatic monoxygenase enzymes. The extent and direction of interactions between the different antiepileptic drugs are varied and unpredictable. Interactions in which the metabolism of phenobarbital, phenytoin or carbamazepine is inhibited are particularly important since these are commonly associated with toxicity. Some inhibitory drugs include macrolide antibiotics, chloramphenicol, cimetidine, isoniazid and numerous sulphonamides. A reduction in efficacy of antibiotic, cardiovascular, corticosteroid, oral anticoagulant and oral contraceptive drugs occurs during combination therapy with enzyme-inducing antiepileptic drugs. Discontinuation of the enzyme inducer or inhibitor will influence the concentrations of the remaining drug(s) and may necessitate dosage readjustment.

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Simultaneous determination of antiepileptic drugs and their two active metabolites by HPLC

Budáková¹,

Brozmanová

Grundmann

et al. 2008

J of Separation Science

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An HPLC procedure for the determination of lamotrigine (LAM) simultaneously with other antiepileptic drugs, primidone (PD), phenobarbital (PB), phenytoin (DPH), carbamazepine (CMZ), and two active metabolites 2-phenyl-2-ethyl-malonamide (PEMA) and 10,11-dihydro-10,11-epoxycarbamazepine (EPO) was developed and validated. The method involves an ordinary RP system and a liquid-liquid extraction. The mobile phase consisting of water/ACN/methanol/triethylamine in the ratio 72:23:5:0.1 with pH 7.0 was selected as the best one after the assays testing both pH and triethylamine contents. UV detection was carried out at a wavelength of 220 nm and the whole analysis took 15 min. The method was linear in the range of 0.5-25 mg/L for PEMA and LAM; 1.25-25 mg/L for PD and CMZ; 0.625-12.5 mg/L for EPO; 1.5-60 mg/L for PB; and 1.25-50 mg/L for DPH, respectively. Within-day CV% and between-day CV% were within 10%. The developed HPLC method can be used for routine therapeutic drug monitoring both in children and adults.

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The effects of phenytoin on phenobarbitone and primidone metabolism.

Cited by 19 publications

References 8 publications

Phenobarbital Pharmacokinetics in Old Age: A Case‐matched Evaluation Based on Therapeutic Drug Monitoring Data

Phenobarbital Pharmacokinetics in Old Age: A Case‐matched Evaluation Based on Therapeutic Drug Monitoring Data

Antiepileptic Drugs

Simultaneous determination of antiepileptic drugs and their two active metabolites by HPLC

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