Tolerability, pharmacokinetics, and neuroendocrine effects of PRX-00023, a novel 5-HT1A agonist, in healthy subjects.
PRX-00023 is a novel, nonazapirone 5-HT1A agonist in clinical development for treatment of affective disorders. The objectives of the initial clinical phase I studies (a single ascending dose study and multiple dose-ascending and high-dose titration studies) were to measure the pharmacokinetics, pharmacodynamic (neuroendocrine) effects, and tolerability of PRX-00023 in healthy subjects. The studies evaluated 10-mg to 150-mg doses of PRX-00023 in up to 112 healthy male and female subjects aged 18 to 54 years. Single and multiple oral doses of PRX-00023 were found to be safe and well tolerated in healthy subjects. PRX-00023 was absorbed relatively rapidly, with a tmax of 0.5 to 2 hours, and eliminated with a half-life of approximately 12 hours. PRX-00023 treatment transiently increased blood prolactin levels 2 to 3 hours after administration, consistent with its mechanism as a 5-HT1A agonist.
Iyer
Ganesh R
GR
Epix Pharmaceuticals, 4 Maguire Road, Lexington, MA 02421, USA. giyer@epixpharma.com
Reinhard
John F
JF
Oshana
Scott
S
Kauffman
Michael
M
Donahue
Stephen
S
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D058825:Serotonin 5-HT1 Receptor Agonists; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000928:Antidepressive Agents; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D013449:Sulfonamides; D011388:Prolactin; C511631:naluzotan