Results
Your Query
▶
▶
Subject | Predicate | Object |
---|---|---|
http://purl.uniprot.org/citations/15179406 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/15179406 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundThe metabolizing enzyme cytochrome P450 (CYP) 3A5 is polymorphically expressed as a result of genetic variants that do not encode functional protein. Because of overlapping substrate specificity with CYP3A4 and the multidrug efflux pump P-glycoprotein, the importance of CYP3A5 genetic polymorphism for pharmacokinetics is controversial.ObjectiveOur objective was to determine whether genetic polymorphisms in CYP3A5 or MDR-1 (which encodes P-glycoprotein) influence the drug levels of ABT-773, a ketolide antibiotic that is a substrate for both CYP3A and P-glycoprotein.MethodsHealthy volunteers given 3 different oral dose levels of ABT-773 were genotyped at 2 common CYP3A5 and 7 common MDR-1 polymorphisms. Individuals were categorized as CYP3A5-positive if they carried at least 1 functional CYP3A5*1 allele and as CYP3A5-negative if they did not. Area under the plasma concentration-time curves (AUCs) from 0 to 6 hours (AUC(t)) and maximum postdose plasma concentration (C(max)) after a single dose and on day 5 of a twice-daily regimen were calculated and correlated with genotypes.ResultsABT-773 AUC(t) and C(max) were, on average, higher in CYP3A5-negative subjects given 450 mg ABT-773 (n = 9) than in CYP3A5-positive subjects with identical doses (n = 8). The relationship for AUC(t) was statistically significant both after a single dose (geometric mean and 95% confidence interval [CI], 5.0 microg.h/mL [3.9-6.4 microg.h/mL] versus 2.8 microg.h/mL [1.8-4.3 microg.h/mL]; P =.03) and on the fifth day of twice-daily dosing (12.4 microg.h/mL [8.7-17.6 microg.h/mL] versus 7.4 microg.h/mL [5.5-9.8 microg.h/mL], P =.04). The relationship for C(max) was statistically significant after a single dose (1220 microg/mL [867-1167 microg/mL] versus 727 microg/mL [506-1044 microg/mL], P =.04) and showed a trend in the same direction on the fifth day of twice-daily dosing (2566 microg/mL [1813-3631 microg/mL] versus 1621 microg/mL [1122-2343 microg/mL], P =.07). In contrast, AUC(t) and C(max) were not significantly different between CYP3A5-positive and CYP3A5-negative individuals given 150 mg or 300 mg ABT-773. ABT-773 plasma levels did not trend with MDR-1 genotypes.ConclusionsThese results suggest that CYP3A5 genotype may be an important determinant of in vivo drug disposition and that this effect may be dose-dependent."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.clpt.2004.01.013"xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Williams L.A."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Ye X."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Grimm D.R."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Katz D.A."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Cassar S.C."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Bukofzer S."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Driscoll R.M."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Gentile M.C."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Gordon E.F."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Gustavson L.E."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "O'dea R.F."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Polzin J.E."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/author | "Rieser M.J."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/name | "Clin Pharmacol Ther"xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/pages | "516-528"xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/title | "CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels."xsd:string |
http://purl.uniprot.org/citations/15179406 | http://purl.uniprot.org/core/volume | "75"xsd:string |
http://purl.uniprot.org/citations/15179406 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15179406 |
http://purl.uniprot.org/citations/15179406 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15179406 |
http://purl.uniprot.org/uniprot/#_F4ZUY5-mappedCitation-15179406 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15179406 |
http://purl.uniprot.org/uniprot/#_Q14V85-mappedCitation-15179406 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15179406 |