Biomaterial Database

Pharmacokinetics, safety, and pharmacologic effects of OPC-21268, a nonpeptide orally active vasopressin V1 receptor antagonist, in humans. 1993

A Ohnishi, and Y Ko, and H Fujihara, and G Miyamoto, and K Okada, and M Odomi

Department of Internal Medicine (I), Daisan Hospital, Jikei University, School of Medicine, Tokyo, Japan.

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)

UI	MeSH Term	Description	Entries
D007564	Japan	A country in eastern Asia, island chain between the North Pacific Ocean and the Sea of Japan, east of the Korean Peninsula. The capital is Tokyo.	Bonin Islands
D008297	Male		Males
D010880	Piperidines	A family of hexahydropyridines.
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D014667	Vasopressins	Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure.	Antidiuretic Hormone,Antidiuretic Hormones,beta-Hypophamine,Pitressin,Vasopressin,Vasopressin (USP),Hormone, Antidiuretic,beta Hypophamine
D015363	Quinolones	A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.	Ketoquinoline,Ketoquinolines,Oxoquinoline,Oxoquinolines,Quinolinone,Quinolinones,Quinolone
D016037	Single-Blind Method	A method in which either the observer(s) or the subject(s) is kept ignorant of the group to which the subjects are assigned.	Single-Masked Study,Single-Blind Study,Single-Masked Method,Method, Single-Blind,Method, Single-Masked,Methods, Single-Blind,Methods, Single-Masked,Single Blind Method,Single Blind Study,Single Masked Method,Single Masked Study,Single-Blind Methods,Single-Blind Studies,Single-Masked Methods,Single-Masked Studies,Studies, Single-Blind,Studies, Single-Masked,Study, Single-Blind,Study, Single-Masked