Abstract
Avitriptan is a new 5-HT1-like agonist with abortive antimigraine properties. The study was conducted to characterize the pharmacokinetics, absolute bioavailability, and disposition of avitriptan after intravenous (iv) and oral administrations of [14C]avitriptan in rats and oral administration of [14C]avitriptan in humans. The doses used were 20 mg/kg iv and oral in the rat, 10 mg iv in humans, and 50 mg oral in humans. The drug was rapidly absorbed after oral administration, with peak plasma concentrations occurring at 0.5 hr postdose. Absolute bioavailability was 19.3% in rats and 17.2% in humans. Renal excretion was a minor route of elimination in both species, with the majority of the dose being excreted in the feces. After a single oral dose, urinary excretion accounted for 10% of the administered dose in rats and 18% of the administered dose in humans, with the remainder excreted in the feces. Extensive biliary excretion was observed in rats. Avitriptan was extensively metabolized after oral administration, with the unchanged drug accounting for 32% and 22% of the total radioactivity in plasma in rats and humans, respectively. Plasma terminal elimination half-life was ∼1 hr in rats and ∼5 hr in humans. The drug was extensively distributed in rat tissues, with a tendency to accumulate in the pigmented tissues of the eye.
Footnotes
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Send reprint requests to: Dr. P. H. Marathe, Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543.
- Abbreviations used are::
- 5-HT
- 5-hydroxytryptamine
- AV
- arteriovenous
- SD
- Sprague Dawley
- Cmax
- maximum plasma concentration
- AUC
- area under the plasma concentration-time curve
- iv
- intravenous
- LE
- Long Evans
- ia
- intraarterial
- LLQ
- lower limit of quantitation
- CSF
- cerebrospinal fluid
- QC
- quality control
- cpm
- counts per minute
- AUC(INF)
- area under the plasma concentration-time curve from 0 to infinity
- t1/2
- terminal elimination half-life
- tmax
- time to maximum concentration
- Received December 3, 1996.
- Accepted March 17, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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