Single dose pharmacokinetics of sumatriptan in healthy volunteers
- 189 Downloads
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 bioavilability 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 1) 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.
Key wordsSumatriptan pharmacokinetics single dose bioavailability dose proportionality healthy volunteers
Unable to display preview. Download preview PDF.
- 1.Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena R (1986) Proposal for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25: 563–576Google Scholar
- 2.Humphrey PPA, Feniuk W, Perren MJ, Connor HE, Oxford AW, Coates IH, Butina D (1988) GR43175, a selective agonist for the 5-HT1-like receptor in dog isolated saphenous vein. Br J Pharmacol 94: 1123–1132Google Scholar
- 3.Ferrari M, Bayliss EM, Ludlow S, Pilgrim AJ (1989) Subcutaneous GR43 175 in the treatment of acute migraine. Cephalagia 9 [Suppl 10]: 348Google Scholar
- 4.Byer J, Gutterman DL, Platchetka JR, Bhattacharyya H (1989) Dose response study for subcutaneous GR43 175 in the treatment of acute migraine. Cephalagia 9 [Suppl 10]: 349–350Google Scholar
- 5.Dahlof C, Winter P, Ludlow S (1989) Oral GR43175, a 5HT1-like agonist, for treatment of the acute migraine attack: an international study-preliminary results. Cephalagia 9 [Suppl 10]: 351Google Scholar
- 6.Ekbom K, Monstad I, Prusinski A, et al (1993) Subcutaneous sumatriptan in the acute treatment of cluster headache; a dose comparison study. Acta Neurol Scand 88: 63–69Google Scholar
- 7.Dixon CM, Saynor DA, Andrew PD, Oxford J, Bradbury A, Tarbit MH (1993) Disposition of sumatriptan in laboratory animals and man. Drug Metab Dispos 21: 761–769Google Scholar
- 8.Andrew PD, Birch HL, Phillpot DA (1993) Determination of sumatriptan succinate in plasma and urine by high-performance liquid chromatography with electrochemical detection. J Pharm Sci 82: 73–76Google Scholar
- 9.Armitage P, Berry G (1987) Statistical methods in medical research. Blackwell, OxfordGoogle Scholar
- 10.Conover WJ (1980) Practical non-parametric statistics. Wiley, New YorkGoogle Scholar
- 11.Tansey MJB, Pilgrim AJ, Lloyd K (1993) Sumatriptan in the acute treatment of migraine. J Neurol Sci 114: 109–116Google Scholar
- 12.Gibaldi M (1984) Pharmacokinetic variability — body weight, age, sex, and genetic factors. In: Biopharmaceutics and clinical pharmacokinetics, 3rd edn. Lea & Febiger, Philadelphia, pp 206–227Google Scholar
- 13.Hussey EK, Donn KH, Busch MA, Fox AW, Powell JR (1991) Pharmacokinetics (PK) of oral sumatriptan in migraine patients during an attack and while painfree (abstract). Clin Pharmacol Ther 49: PI-46Google Scholar
- 14.Zanchin G (1993) Oral sumatriptan in the acute treatment of migraine (abstract). Can J Neurol Sci 20 [Suppl 4]: no. 1-14-36, S37Google Scholar