Pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, in humans.
The pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, have been investigated in 33 healthy subjects. First, 24 subjects were randomly divided into 3 groups of 8, 6 of whom were given 2 ascending single oral doses out of 6 (10, 50, 150, 300, 450, and 600 mg) of OPC-21268 after an overnight fast. The remaining two subjects in each group received placebo as control at each dosing. Additionally, after this procedure, the 6 subjects who received 50-mg single doses were given the same dose in a nonfasting condition. After the single-dose study was completed and the safety and tolerability were ascertained, the remaining 9 subjects, including 3 controls, were given 300 mg of the drug 3 times daily for 7 days (days 3-9) and were given single 100-mg oral doses before (day 1) and after (day 10) this repeated-dose study. OPC-21268 plasma concentrations declined in a monoexponential or biexponential pattern after reaching the maximum plasma concentrations (Cmax). The mean (+/- standard error of the mean) plasma half-life (t1/2) of the alpha phase ranged from 1.31 +/- 0.11 to 1.78 +/- 0.15 hours, and the mean t1/2 of the beta phase ranged from 4.31 +/- 0.28 to 6.28 +/- 0.59 hours. The area under the concentration (AUC0-infinity) and Cmax were proportional to the dose (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine (I), Daisan Hospital, Jikei University, School of Medicine, Tokyo, Japan.
A
A
Ohnishi
Y
Y
Ko
H
H
Fujihara
G
G
Miyamoto
K
K
Okada
M
M
Odomi
D000284:Administration, Oral; D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D004334:Drug Administration Schedule; D006801:Humans; D007564:Japan; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D015363:Quinolones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D016037:Single-Blind Method; D014667:Vasopressins / Q000097:blood / Q000652:urine
D065092:Antidiuretic Hormone Receptor Antagonists; D010880:Piperidines; D015363:Quinolones; D014667:Vasopressins; C068644:OPC 21268