Premium
Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man.
Author(s) -
Macphee GJ,
Mitchell JR,
Wiseman L,
McLellan AR,
Park BK,
McInnes GT,
Brodie MJ
Publication year - 1988
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.1365-2125.1988.tb03282.x
Subject(s) - carbamazepine , pharmacokinetics , crossover study , anticonvulsant , free fraction , pharmacology , valproic acid , chemistry , placebo , medicine , epilepsy , alternative medicine , pathology , psychiatry
1 The effect of sodium valproate (VPA; 500 mg thrice daily for 7 days) and matched placebo on the disposition and psychomotor profile of a single dose of carbamazepine (CBZ; 10 mg kg‐1) was studied in eight healthy male subjects using a randomised balanced crossover design. 2 VPA alone had no effect on antipyrine clearance, urinary 6 beta‐ hydroxycortisol excretion and a battery of psychomotor function tests after 3 days' treatment despite achieving a mean steady‐state concentration (90 +/− 6 mg 1(‐1)) well within the target range (50‐100 mg 1(‐1)) for the drug. 3 VPA pre‐treatment did not alter total CBZ area under the concentration‐time curve (AUC 0‐59 h) but did prolong CBZ elimination half life by 12% (P less than 0.01). AUC 0‐59 h for free plasma CBZ was 13% higher (P less than 0.02) and half‐life of unbound CBZ 16% longer (P less than 0.02) during VPA treatment. CBZ‐ 10,11 epoxide (CBZ‐E) levels (52%) and CBZ‐E/CBZ ratios (45%) were both elevated by concurrent VPA (P less than 0.05) and free CBZ fraction was increased by 7% (P less than 0.02). 4 The sole effect of VPA on the psychomotor profile of CBZ was prolongation of card sorting time (P less than 0.05), although CBZ‐related side effects were reported as more severe when VPA was also taken (P less than 0.01). 5 These data suggest that VPA displaces CBZ from plasma protein binding sites and inhibits the metabolism of both the parent drug and its epoxide.(ABSTRACT TRUNCATED AT 250 WORDS)