Bioavailability of terfenadine in man

Abstract

Fourteen normal male subjects were given either 60mg or 180mg of terfenadine suspension in a randomized two-way crossover study. Peak plasma concentrations of 1.544 +/- 0.726 (mean +/- S.D.) ng ml-1 were obtained in 0.786 h following the 60 mg dose and displayed an AUC or 11.864 +/- 3.369 ng h ml-1. Whereas peak plasma concentrations of 4.519 +/- 2.002 ng ml-1 in 1.071 +/- 0.514 h were obtained following the 180 mg dose. The AUC following the 180 mg dose was 44.341 +/- 22.041 ng h ml-1. When 60 mg of 14C terfenadine was given to six additional subjects, the peak plasma concentrations of 351 +/- 43 ng equivalents per ml were obtained in 1.67 +/- 0.41 h and the AUC was 2297.71 +/- 310.85 ng-equivalents h ml-1. This indicates that approximately 99.5 per cent of the terfenadine related material that is absorbed undergoes biotransformation. Urinary excretion of 14C accounted for 39.89 +/- 5.29 per cent of the dose while 60.58 +/- 2.44 per cent of the dose was recovered in the feces in twelve days. Thin-layer chromatographic (TLC) examination of fecal extracts showed only a trace of material chromatographing with terfenadine. This may indicate that the 14C present in the feces is not due to lack of absorption.

The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo

“…For CYP3A substrates with a low clearance and high oral availability such as alprazolam, 55 an increased oral clearance will be expected because of the hepatic induction of CYP3A by echinacea. In contrast, for CYP3A substrates such as buspirone, 56 simvastatin, 57 and terfenadine, 58 which have low oral bioavailabilities (<5%) as a result of substantial intestinal first‐pass metabolism, concurrent echinacea administration may result in increased serum concentrations of these substrates as a result of the predominant effect of intestinal CYP3A inhibition.…”

Hepatobiliary Disposition of a Drug/Metabolite Pair: Comprehensive Pharmacokinetic Modeling in Sandwich-Cultured Rat Hepatocytes

“…However, the rate constants for terfenadine uptake (k TERM3 C ) and excretion (k TERC3 M ) across the basolateral membrane were approximately equal (Table 3), consistent with a predominant diffusional mechanism of TER flux across this membrane. A diffusional process for terfenadine accumulation is consistent with nearly 100% absorption of terfenadine after oral administration in humans (Okerholm et al, 1981).…”

The psychomotor and cognitive effects of a new antihistamine, mizolastine, compared to terfenadine, triprolidine and placebo in healthy volunteers

“…The pharmacokinetics of the drugs were taken into account when deciding the test times. Mizolastine is rapidly absorbed, with tma × of 1.4 h and elimination T1/2 of 14 h; terfenadine reaches peak plasma concentration at 1-2 h and has a biphasic elimination, with half lives of 3.6 and 16-23 h (Okerholm et al 1981); triprolidine reaches peak plasma concentration at 2 h and has a half life of around 2 h (Drouin 1985). Before the experiment, subjects were trained to a plateau of performance on the tests.…”

“…The present experiment was designed to test whether the substance affects the psychomotor skills necessary for the safe conduct of the activities of everyday life. Triprolidine was included as a positive internal control (verum) because of its known sedative effects (Keith et al 1986;Rombaut et al 1991;Volkerts et al 1992); terfenadine was also included as a negative control as it was expected not to have sedative properties, due to non-penetration of the blood-brain barrier (McTavish et al 1990;Okerholm et al 1981;Sorkin and Heel 1985).…”