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Initial human experience with MK‐462 (rizatriptan): a novel 5=HT ID agonist
Author(s) -
Sciberras David G.,
Polvino William J.,
Gertz Barry J.,
Cheng Haiyung,
Stepanavage Michael,
Wittreich Johanna,
Olah Timothy,
Edwards Mark,
Mant Timothy
Publication year - 1997
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.1365-2125.1997.tb00137.x
Subject(s) - sumatriptan , placebo , pharmacokinetics , rizatriptan , agonist , medicine , crossover study , migraine , pharmacodynamics , oral administration , heart rate , blood pressure , anesthesia , endocrinology , receptor , alternative medicine , pathology
Aim We evaluated the pharmacokinetics and pharmacodynamics of oral MK‐462 in comparison with oral sumatriptan in healthy male volunteers. Methods Sixteen healthy male volunteers were studied in a rising, single dose, alternating panel design with eight subjects per panel. Matching placebo was administered to two of eight study subjects at each dose level of MK‐462 in a randomized, double‐blind fashion. Results MK‐462 was rapidly absorbed with a median t max of 1.3 h (range 1–3 h) vs a t max for sumatriptan of 2.5 h (range 1–4 h, P < 0.001). Administration of either MK‐462 or sumatriptan produced maximal mean elevations of 5–10 mmHg in systolic and diastolic blood pressures without effect on heart rate; the changes occurred sooner following MK‐462, consistent with more rapid absorption. Both MK‐462 and sumatriptan provoked mild increases in serum growth hormone without any effect on serum prolactin concentrations. The most commonly reported symptom following MK‐462 was drowsiness. Conclusions These results indicate that the novel 5‐HT 1D agonist, MK‐462, is rapidly absorbed following oral administration and warrants further investigation of its utility in the treatment of acute migraine.