A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.
Br J Clin Pharmacol
; 67(3): 288-98, 2009 Mar.
Article
em En
| MEDLINE
| ID: mdl-19523012
ABSTRACT
AIMS:
To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg).METHODS:
Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy.RESULTS:
The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2.CONCLUSIONS:
Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antagonistas dos Receptores Histamínicos H1
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article