Absorption, pharmacokinetics and metabolism of ¹⁴C-sumatriptan following intranasal administration to the rat

Abstract

1. Studies have been carried out to investigate the absorption of sumatriptan after intranasal administration to rats. The pharmacokinetics, metabolism and excretion of ¹⁴C-sumatriptan were compared following intranasal and intravenous dosing to male and female albino rats using an aqueous buffered formulation at pH 5.5.

2. Following intravenous administration sumatriptan was eliminated from plasma with a half-life of about 1.1 h. After intranasal administration there was rapid absorption of part of the dose and two peak plasma concentrations were observed, initially at 0.5 and then at 1.5–2 h. The elimination half-life after the second peak was estimated as being about 4 h.

3. Radioactivity was largely excreted in urine (up to 89% of dose in 168 h) after both intravenous and intranasal administration, with a faster rate of excretion after intravenous dosage (73% males, 64% females within 6 h) than after intranasal dosage (37% males, 40% females within 6 h).

4. ¹⁴C-sumatriptan was the major component in urine and in extracts of faeces after both intravenous and intranasal administration. The major metabolite excreted in urine and faeces was GR49336, the indole acetic acid analogue.

5. The results of this in vivo rat study suggest that absorption of the dose via the nasal mucosa is incomplete after intranasal administration and that there is a secondary absorption phase probably reflecting oral absorption of part of the dose. The bioavailability is estimated as about 30%, for the period 0–6 h.