Lack of effect of terfenadine on the pharmacokinetics of the CYP3A4 substrate buspirone.
The effects of terfenadine, a non-sedating antihistamine on the pharmacokinetics and pharmacodynamics of buspirone, a CYP3A4 substrate, were investigated in a randomised, placebo-controlled, two-phase cross-over study. Ten healthy volunteers took either 120 mg terfenadine or matched placebo orally once daily for 3 days. On day 3, 10 mg buspirone was taken orally. Plasma concentrations of buspirone were measured up to 18 hr and its pharmacodynamic effects up to 8 hr. Terfenadine slightly but not significantly increased plasma concentrations of buspirone. No psychomotor deterioration was observed during the terfenadine phase. In conclusion, terfenadine did not significantly affect the pharmacokinetics of buspirone, a CYP3A4 substrate shown to be very susceptible to interactions with CYP3A4 inhibitors. Thus, terfenadine is expected to have little effect on the pharmacokinetics of CYP3A4 substrates in general.
Lamberg
T S
TS
Department of Clinical Pharmacology, University of Helsinki, Finland.
Kivistö
K T
KT
Neuvonen
P J
PJ
D000328:Adult; D002065:Buspirone / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000187:drug effects* / Q000378:metabolism; D016593:Terfenadine / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D016593:Terfenadine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002065:Buspirone