Single dose pharmacokinetics of sumatriptan in healthy volunteers

Abstract

Sumatriptan is classified as a vascular 5HT1 receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration. The mean subcutaneous bioavailability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception 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 pharmacologically 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 glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 l) and an elimination half-life of 2 h. Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.

Formulation and Optimization of Orally Disintegrating Tablets of Sumatriptan Succinate

“…The results are in line with the findings reported by other researchers. [31][32][33][34] The possible reason for the appearance of double peaks in many rabbits could be to the presence of two compartment absorption phases with only one disposition phase. 35,36) The probable reasons for multiple peaks may be due to alteration in the gastric motility by sumatriptan 37,38) and/or presence of multiple absorption sites for sumatriptan in the gastrointestinal tract of rabbits.…”

Distribution and excretion of sumatriptan in human milk

“…The broad elevated concentration-time profile between 1-5 h (generally>50 pg 1-I), with a mean time of peak concentration in the milk of 2.6 h, was ** assuming bioavailability is essentially complete [ 71 unexpected. However, others have shown that following oral administration, peak plasma concentrations do not occur until 1-4 h after dose [5,7,12]. They suggested that the late peak was in part due to extensive first-pass metabolism and in part due to incomplete absorption.…”

Determination of sumatriptan in human plasma using liquid chromatography-mass spectrometry for pharmacokinetic study in healthy Korean volunteers

“…[5] To develop appropriate individualized treatment strategies, it is important to understand the effects of covariates such as body weight, race, and sex on the pharmacokinetics. [6,7] Recently Munjal et al examined the impact of these covariates on the plasma concentration profile of subcutaneous sumatriptan.…”