Reduced felodipine bioavailability in patients taking anticonvulsants.
Felodipine is a dihydropyridine calcium antagonist, structurally related to nifedipine, which undergoes extensive first-pass hepatic metabolism and normally has an oral bioavailability of 15%. Felodipine disposition was studied in 10 patients who had microsomal enzyme induction due to chronic anticonvulsant therapy, and in 12 normal volunteers matched for age and sex. Plasma felodipine concentrations after a 5 mg oral dose were grossly reduced in the epileptic patients: the mean peak concentration was 1.6 (vs 8.9) nmol/l, and the area under the curve was only 2.0 (vs 30.0) nmol.h/l. The relative bioavailability of felodipine in the epileptic patients was thus only 6.6% of that in the normal subjects, and less than 1% of the oral dose was systemically available. Patients on anticonvulsant treatment will require substantially higher doses of felodipine to achieve plasma concentrations equivalent to those in non-induced subjects.
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D000983:Antipyrine / Q000097:blood; D001682:Biological Availability; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D015736:Felodipine; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009568:Nitrendipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005723:gamma-Glutamyltransferase / Q000097:blood
D000927:Anticonvulsants; D009568:Nitrendipine; D005723:gamma-Glutamyltransferase; D015736:Felodipine; D000983:Antipyrine