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Inhibition of phenobarbitone N‐glucosidation by valproate.
Author(s) -
Bernus I,
Dickinson RG,
Hooper WD,
Eadie MJ
Publication year - 1994
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1994.tb04375.x
Subject(s) - phenobarbital , excretion , glucuronidation , chemistry , valproic acid , anticonvulsant , urinary system , medicine , endocrinology , pharmacology , epilepsy , microsome , biochemistry , enzyme , psychiatry
Plasma phenobarbitone concentrations and daily urinary excretion of phenobarbitone and its metabolites p‐hydroxyphenobarbitone (conjugated and unconjugated), and [S]‐phenobarbitone‐N‐glucoside were measured under steady‐state conditions in two groups of epileptic patients, (i) taking phenobarbitone with or without other drugs, but not valproate (n = 12), and (ii) taking phenobarbitone with other drugs including valproate (n = 8). Mean steady‐state plasma phenobarbitone concentrations were 5.9 mg l‐1 higher, relative to drug dose, in the patients taking valproate than in those not taking valproate. Urinary excretion of [S]‐phenobarbitone‐N‐glucoside was significantly lower in the group taking valproate (1.9 +/‐ s.d. 2.0% of phenobarbitone dose vs 16.2 +/‐ s.d. 9.9%). Urinary excretion of phenobarbitone (23.7 +/‐ s.d. 9.8% vs 48.2 +/‐ s.d. 13.6%) and unconjugated p‐hydroxyphenobarbitone (5.7 +/‐ s.d. 3.9% vs 16.0 +/‐ s.d. 9.1%) was higher in those taking valproate, while conjugated p‐hydroxyphenobarbitone excretion was similar in both groups (8.3 +/‐ s.d. 4.9% vs 6.5 +/‐ s.d. 2.9%). Valproate appeared to inhibit both the direct N‐glucosidation of phenobarbitone and the O‐glucuronidation of p‐hydroxyphenobarbitone.