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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1995-3-10
|
| pubmed:abstractText |
The pharmacokinetic (PK) characteristics of KNI-272, a potent and selective HIV-1 protease inhibitor, were evaluated in rats after intravenous (IV) administration. The effect of dose on KNI-272 plasma kinetics, and the urinary and biliary elimination kinetics of KNI-272, were examined. After IV administration of 10.0 mg kg-1 KNI-272, the mean terminal elimination half-life, t1/2 lambda zeta, was 3.49 +/- 0.19 (SE) h, the total plasma clearance, CLtot, was 15.1 +/- 1.2 mL min-1 and the distribution volume at steady state, Vd,ss, was 3790 +/- 280 mL kg-1. On the other hand, after 1.0 mg kg-1 IV administration, t1/2 lambda zeta was 3.04 +/- 0.11 h, CLtot was 15.9 +/- 0.2 mL min-1, and Vd,ss was 6950 +/- 600 mL kg-1. The PK parameters of KNI-272 after IV administration showed that the disposition of KNI-272 in the rat plasma is linear within the dose range from 1.0 to 10.0 mg kg-1. Using an equilibrium dialysis method, the plasma binding of KNI-272 was measured in vitro. The free fractions were 17.7 +/- 0.6%, 12.1 +/- 1.5%, and 13.8 +/- 1.4% at the total concentration ranges of 9.898 +/- 0.097 microgram mL-1, 0.888 +/- 0.008 microgram mL-1, and 0.470 +/- 0.55 microgram mL-1, respectively. The percentages of the dose excreted into the urine and bile as the unchanged form were 1.20 +/- 1.06% and 1.61 +/- 0.32% at 1.0 mg kg-1 dose, and 0.164 +/- 0.083% and 1.42 +/- 0.26% at 10.0 mg kg-1 dose, respectively. The renal clearance (CLR) and the biliary clearance (CLB) were calculated to be 0.191 and 0.256 mL min-1 for 1.0 mg kg-1, and 0.0248 and 0.215 mL min-1 for 10.0 mg kg-1, respectively. When comparing these values with the CLtot values, the urinary and biliary excretion of KNI-272 are minor disposition routes.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HIV Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/kynostatin 272
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0142-2782
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
15
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
617-26
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7849237-Animals,
pubmed-meshheading:7849237-Antiviral Agents,
pubmed-meshheading:7849237-Bile,
pubmed-meshheading:7849237-Blood Proteins,
pubmed-meshheading:7849237-Calibration,
pubmed-meshheading:7849237-Chromatography, High Pressure Liquid,
pubmed-meshheading:7849237-Dialysis,
pubmed-meshheading:7849237-Dose-Response Relationship, Drug,
pubmed-meshheading:7849237-HIV Protease Inhibitors,
pubmed-meshheading:7849237-Half-Life,
pubmed-meshheading:7849237-Injections, Intravenous,
pubmed-meshheading:7849237-Male,
pubmed-meshheading:7849237-Models, Theoretical,
pubmed-meshheading:7849237-Oligopeptides,
pubmed-meshheading:7849237-Protein Binding,
pubmed-meshheading:7849237-Rats,
pubmed-meshheading:7849237-Rats, Wistar,
pubmed-meshheading:7849237-Reference Standards,
pubmed-meshheading:7849237-Reproducibility of Results
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Plasma pharmacokinetics and urinary and biliary excretion of a new potent tripeptide HIV-1 protease inhibitor, KNI-272, in rats after intravenous administration.
|
| pubmed:affiliation |
Department of Pharmaceutics and Pharmacokinetics, Kyoto Pharmaceutical University, Japan.
|
| pubmed:publicationType |
Journal Article,
In Vitro
|