SINGLE-DOSE PHARMACOKINETICS OF SUMATRIPTAN IN HEALTHY-VOLUNTEERS

Sumatriptan is classified as a vascular 5HT(1) receptor agonist and is effective in the acute treatment of migraine and cluster headache. Su matriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of suma triptan differ depending on the route of administration. The mean subc utaneous bioavilability is 96% compared to 14% for the oral tablet. Th e lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject. variability in plasma suma triptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is ach ieved following subcutaneous dosing, The pharmacokinetics of sumatript an are linear up to a subcutaneous dose of 16 mg. Following oral dosin g up to 400 mg, the pharmacokinetics are also linear, with the excepti on of rate of absorption, as indicated by a dose dependent increase in time to peak concentration. Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharma cologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glo merular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of di stribution (1701) and an elimination half-life of 2 h. Oral doses of s umatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practic e, sumatriptan is administered as a film coated tablet or by subcutane ous injection into the thigh.