Linked Life Data

9570002

Source:http://linkedlifedata.com/resource/pubmed/id/9570002

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-6-8
pubmed:abstractText
The purpose of this study was to characterize CI-992 pharmacokinetics and pharmacokinetics/pharmacodynamics (PK/PD) in sodium deplete monkeys. Panels of monkeys were administered CI-992 as a 1 h intravenous infusions (0.1 and 1 mg kg-1) or as single oral doses (0, 10, 50, and 100 mg kg-1). Mean arterial blood pressure (MABP) was monitored and serial blood samples were collected up to 24 h postdose. Plasma CI-992 concentrations were quantitated by radioimmunoassay. Pharmacokinetic parameters were calculated by noncompartmental methods. PK/PD relationships were assessed by standard methods. Oral bioavailability of CI-992 in the monkeys was < 2%; steady-state volume of distribution was 0.67 L kg-1; clearance was 10.4 mL min-1 kg-1. Following oral administration, tmax generally occurred 6-9 h postadministration; plasma CI-992 concentrations increased with increasing dose between 10 and 50 mg kg-1, but did not change appreciably from 50 to 100 mg kg-1. After intravenous administration, change in MABP was correlated with plasma CI-992 concentration through an effect compartment model in which the maximum achievable effect was a 22 mm Hg decrease in MABP; the steady-state concentration which produced half the maximum effect was 11 ng mL-1. Following the 10 mg kg-1 oral dose the maximum decrease in MABP was 19.1 mm Hg; higher doses did not produce greater maximum response but increased the duration of action. In contrast to observations following intravenous administration, a trend for decreasing MABP with increasing plasma CI-992 was not apparent following oral CI-992 administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0142-2782
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-91
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Pharmacokinetics and pharmacodynamics of CI-992 following intravenous and oral administration to cynomolgus monkeys.
pubmed:affiliation
Department of Pharmacology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA. cookj@aa.wl.com
pubmed:publicationType
Journal Article