A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients.
The antipyrine clearance and the urinary excretion of D-glucaric acid (D-GA) were determined in 122 patients receiving chronic anticonvulsant drug treatment and in 21 drug-free control subjects. Patients treated with carbamazepine (CBZ), phenytoin (DPH), primidone (PMD) and phenobarbitone (PB), either alone or in combination, showed higher values of antipyrine clearance and excreted larger amounts of D-GA as compared to controls. While antipyrine clearance values did not differ significantly from one drug group to another, D-GA excretion was significantly higher in patients treated with CBZ than in those treated with DPH. In patients treated with sodium valproate antipyrine clearance did not differ from control values. There was a trend for D-GA excretion to be higher in these patients but the difference was not statistically significant. Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction. These data demonstrate a dose-dependent degree of enzyme induction in patients receiving therapeutic doses of these anticonvulsants. The relative potency at average dose levels for antipyrine clearance was PB (1), DPH (0.92), CBZ (0.84), PMD (0.82) and for log D-GA excretion was PB (1), CBZ (0.96), PMD (0.95), DPH (0.90).
D000927:Anticonvulsants / Q000378:metabolism / Q000494:pharmacology*; D000983:Antipyrine / Q000378:metabolism; D002220:Carbamazepine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects*; D004827:Epilepsy / Q000201:enzymology*; D005260:Female; D005937:Glucaric Acid / Q000652:urine; D006207:Half-Life; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D011324:Primidone / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D011324:Primidone; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D005937:Glucaric Acid; D000983:Antipyrine; D010634:Phenobarbital