There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED , yet no evidence for absolute efficacy .
No convincing evidence exists for an excess of behavioural adverse effects , over other AEDs , attributable to phenobarbital .
Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs .
This is in contrast to the excess of such adverse effects reported in studies open to observer bias .
However , the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern .
INTRODUCTION : Against a background of concern about the safety of new pharmaceutical products , there has been renewed interest in one of the oldest antiepileptic drugs ( AEDs ) , phenobarbital .
Although still in widespread use in developing countries , its popularity has slipped in Western countries over the past century , partly because of controversy about its adverse effect profile .
This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy .
CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics.
OBJECTIVE The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone ( PB ) using a nonlinear mixed-effects model ( NONMEM ) analysis in Japanese adults with epilepsy . METHODS A total of 144 serum PB concentrations were obtained from 74 subjects treated with both PB and phenytoin but without valproic acid .  All patients were classified into three groups by CYP2C19 genotyping : G1 , G2 and G3 were homozygous for the wild type of CYP2C19 ( * 1/*1 ) , heterozygous extensive metabolizers ( EMs ) , ( * 1/*2 or * 1/*3 ) , and poor metabolizers ( PMs ) , ( * 2/*2 , * 2/*3 ) , respectively . All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype . RESULTS Thirty-three patients belonged to G1 ( 44.6 % ) , 35 to G2 ( 47.3 % ) , and 6 to G3 ( 8.1 % ) . The total clearance ( CL ) of PB significantly decreased by 18.8 % in PMs ( G3 ) relative to EMs ( G1 and G2 ) . The CL tended to be lower in G2 than in G1 . CONCLUSION In this study , we first demonstrated the effect of the CYP2C19 polymorphism on pharmacokinetics of PB by genotyping . The contribution of other metabolic enzymes in the metabolism of PB in humans remains to be eluci date d ; however , it appears that the disposition of PB is mediated in part by this enzyme . The estimated population clearance values in the three genotype groups can be used to predict the PB dose required to achieve an appropriate serum concentration in an individual patient
There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED , yet no evidence for absolute efficacy .
No convincing evidence exists for an excess of behavioural adverse effects , over other AEDs , attributable to phenobarbital .
Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs .
This is in contrast to the excess of such adverse effects reported in studies open to observer bias .
However , the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern .
INTRODUCTION : Against a background of concern about the safety of new pharmaceutical products , there has been renewed interest in one of the oldest antiepileptic drugs ( AEDs ) , phenobarbital .
Although still in widespread use in developing countries , its popularity has slipped in Western countries over the past century , partly because of controversy about its adverse effect profile .
This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy .