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The tolerability and pharmacokinetics of the novel antimigraine compound 311C90 in healthy male volunteers
Author(s) -
SEABER E.,
ON N.,
PHILLIPS S.,
CHURCHUS R.,
POSNER J.,
ROLAN P.
Publication year - 1996
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1996.tb00172.x
Subject(s) - tolerability , pharmacokinetics , pharmacology , cmax , oral administration , agonist , medicine , placebo , migraine , volume of distribution , active metabolite , urine , crossover study , adverse effect , receptor , alternative medicine , pathology
1 311C90 is a novel and selective agonist at 5‐HT 1D receptors, with central and peripheral actions, currently in development for the acute oral treatment of migraine. 2 The pharmacokinetic and tolerability profiles of single oral doses from 1–50 mg 311C90 were investigated in 12 healthy male volunteers in a double‐blind, placebo‐controlled, dose‐escalating study. 3 311C90 was well tolerated with most adverse experiences of mild and transient nature. 4 Absorption was rapid with dose‐independent kinetics. Median t max was 2–4 h although 50–85% of eventual C max was attained within 1 h. The t 1/2 was 2.5‐3 h with a high apparent plasma clearance (CL/F > 2000 ml min ‐1 ) and apparent volume of distribution (V Z /F) of 400–5001. 5 Three metabolites were detected in plasma and urine, one of which, the N ‐desmethyl metabolite, has 5‐HT 1D agonist activity. 6 311C90 showed no clinically significant effects on blood pressure, heart rate, ECG or laboratory variables at any dose and demonstrated a tolerability and pharmacokinetic profile compatible with an acute oral migraine treatment.