Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients.
1. The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2. Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven-fold (P less than 0.01) in patients taking enzyme-inducing anticonvulsants and increased by about 50% (P less than 0.05) in patients taking sodium valproate. 3. Nimodipine half-lives were shorter in enzyme-induced patients than in controls (3.9 +/- 2.0 h vs 9.1 +/- 3.4 h, means +/- s.d., P less than 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate-treated patients, half-lives (8.2 +/- 1.8 h) were similar to those found in controls.
Tartara
A
A
Neurology Clinic C. Mondino, Pavia, Italy.
Galimberti
C A
CA
Manni
R
R
Parietti
L
L
Zucca
C
C
Baasch
H
H
Caresia
L
L
Mück
W
W
Barzaghi
N
N
Gatti
G
G
D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D004347:Drug Interactions; D004790:Enzyme Induction; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009553:Nimodipine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D009553:Nimodipine; D014635:Valproic Acid