Linked Life Data

8452345

Source:http://linkedlifedata.com/resource/pubmed/id/8452345

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-4-15
pubmed:abstractText
Nevirapine, a nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, was administered for the first time to humans in a pilot study designed to investigate the pharmacokinetics and tolerance of the drug following single-dose administration to 21 HIV-1-infected individuals. The study followed a parallel design. Different groups of three subjects each were given one of seven dose levels (2.5 to 400 mg) in sequential order, starting with the lowest dose. Each subject received only one dose. Nevirapine was rapidly absorbed at all doses from a tablet formulation. Peak concentrations in plasma were generally achieved within 90 min of dose administration. Secondary peaks were also noted between 3 and 12 h or between 24 and 28 h, the latter being noted mainly in subjects receiving the higher doses. After 24 h, concentrations in plasma declined in a log-linear fashion. The terminal half-life and mean residence time exceeded 24 h in all but one subject, indicating a prolonged disposition time in this population. Both peak concentrations in plasma and areas under the plasma concentration-time curves increased proportionally with increasing dose from 2.5 to 200 mg; however, the increase in the peak concentration in plasma and the area under the plasma concentration-time curve appeared to be less than proportional at the 400-mg dose level in this small number of subjects. This observation may be due to increased clearance or decreased absorption at the highest dose or population differences in absorption or clearance between doses. Studies with a cross-over design are planned to resolve these issues. The pharmacokinetic characteristics of nevirapine are appropriate for once-daily administration. A daily 12.5-mg dose is predicted to achieve trough concentrations in plasma in the range required to totally inhibit replication of wild-type HIV-1 in human T-cell culture.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0066-4804
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
178-82
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Pharmacokinetics of nevirapine: initial single-rising-dose study in humans.
pubmed:affiliation
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't