Effect of acute and chronic terfenadine on free and total serum phenytoin concentrations in epileptic patients.
Terfenadine is a unique H1-receptor antagonist devoid of adverse central nervous system (CNS) effects. Terfenadine is highly protein bound and has been shown to stimulate hepatic microsomal enzymes, making an interaction with phenytoin (PHT) possible. After assuring constant PHT levels for 7 days, 12 epileptic patients were studied with PHT alone, after a single daily dose of terfenadine (60 mg twice daily), and again after 2 weeks of chronic terfenadine therapy. Samples for PHT were drawn over 24 h, and urine was collected for determination of the PHT metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH). The pharmacokinetic parameters calculated for total and free PHT and HPPH were area under the time concentration curve (AUC), the maximum serum concentration (Cmax), the minimum serum concentration (Cmin), and the percentage of fluctuation between maximum and minimum concentrations. A factor analysis was used to clarify interrelationships. Five dependent variables were found to represent the data. These were assessed by multi-variate analysis of variance (MANOVA); p less than 0.05 was considered significant. No significant differences were observed for any of the parameters for the acute or chronic effects of terfenadine. We conclude that terfenadine does not interfere with PHT.
Coniglio
A A
AA
Department of Pharmacy and Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298-0581.
Garnett
W R
WR
Pellock
J H
JH
Tsidonis
O
O
Hepler
C D
CD
Serafin
R
R
Small
R E
RE
Driscoll
S M
SM
Karnes
H T
HT
D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D004347:Drug Interactions; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010672:Phenytoin / Q000097:blood* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D016593:Terfenadine
D001559:Benzhydryl Compounds; D001798:Blood Proteins; D006634:Histamine H1 Antagonists; D010672:Phenytoin; D016593:Terfenadine