FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1970794988> ?p ?o ?g. }

• W1970794988 endingPage "618" @default.
• W1970794988 startingPage "605" @default.
• W1970794988 abstract "Saquinavir, a widely prescribed human immunodeficiency virus 1 protease inhibitor, has a low and variable oral bioavailability that has been attributed to extensive first-pass extraction mediated by hepatic or intestinal cytochrome P450 (CYP) 3A4 and intestinal P-glycoprotein (P-gp). The polymorphic CYP3A5 has also been shown to influence the saquinavir metabolite/parent urinary ratio, suggesting a role for CYP3A5.Twenty healthy subjects received a single oral dose of saquinavir (600 mg) with water (control) and, on a separate occasion, with Seville orange juice (a selective intestinal CYP3A4/5 inhibitor). Hepatic CYP3A4 activity was evaluated by use of the erythromycin breath test. Duodenal biopsy specimens were used to assess relative intestinal CYP3A4 and CYP3A5 protein contents. Relative P-gp content was also assessed in the biopsy specimens and in lymphocytes. Genetic polymorphisms in MDR1 (in exon 21 and 26), CYP3A5 (*1 and *3), and CYP3A4*1B were identified by direct sequencing. Saquinavir plasma concentrations were measured by tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameter estimates (maximum concentration, time to reach maximum concentration, area under the concentration-time curve, apparent oral clearance [CL/F]) were computed by standard noncompartmental methods. Stepwise multiple regression analysis was used to identify the hepatic or intestinal variables that predicted variation in saquinavir pharmacokinetic measures.Baseline saquinavir CL/F was not correlated with liver CYP3A4 activity (the erythromycin breath test result), intestinal CYP3A4 content, or intestinal P-gp content (r(2) = 0.08, 0.08, and 0.007, respectively; P > .2). MDR1 genotype and lymphocyte P-gp content were also not predictive. Among the 6 subjects expressing intestinal CYP3A5, the mean saquinavir CL/F was almost twice as high as for the 14 nonexpressors (36.7 L/h [95% confidence interval (CI), 18.7-54.6 L/h] and 19.3 L/h [95% CI, 11.2-27.4 L/h], respectively; P = .03). However, among the 6 CYP3A5 expressors, there was an unexpected negative correlation between CL/F and intestinal CYP3A5 content (r(2) = 0.58, P = .05). Seville orange juice decreased the mean CL/F in all 20 subjects from 24.5 L/h (95% CI, 16.7-32.3 L/h) to 14.7 L/h (95% CI, 8.4-20.6 L/h) (P = .05). The effect size did not appear to be influenced by CYP3A5 expression.The CYP3A5*1 genotype is associated with increased saquinavir CL/F. This does not appear to reflect intestinal CYP3A5 expression and presumably reflects the contribution of hepatic CYP3A5. The interaction with Seville orange juice in subjects not expressing CYP3A5 supports a role for intestinal CYP3A4. However, the modest nature of the interaction, combined with the inability to detect a correlation between CL/F and CYP3A4 enterocyte content, supports our recent in vitro work suggesting a smaller contribution of intestinal CYP3A4 than has been assumed." @default.
• W1970794988 created "2016-06-24" @default.
• W1970794988 creator A5003784173 @default.
• W1970794988 creator A5012663330 @default.
• W1970794988 creator A5022078224 @default.
• W1970794988 creator A5025109579 @default.
• W1970794988 creator A5041913194 @default.
• W1970794988 creator A5045272190 @default.
• W1970794988 creator A5054318811 @default.
• W1970794988 creator A5062878299 @default.
• W1970794988 creator A5080434800 @default.
• W1970794988 creator A5083433629 @default.
• W1970794988 date "2005-12-01" @default.
• W1970794988 modified "2023-10-17" @default.
• W1970794988 title "Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5" @default.
• W1970794988 cites W1560709301 @default.
• W1970794988 cites W1571401550 @default.
• W1970794988 cites W165504565 @default.
• W1970794988 cites W1882430758 @default.
• W1970794988 cites W1901300892 @default.
• W1970794988 cites W1929292775 @default.
• W1970794988 cites W1972115776 @default.
• W1970794988 cites W1978470492 @default.
• W1970794988 cites W1982105713 @default.
• W1970794988 cites W1983283139 @default.
• W1970794988 cites W1990732193 @default.
• W1970794988 cites W1999021046 @default.
• W1970794988 cites W2000929966 @default.
• W1970794988 cites W2003862487 @default.
• W1970794988 cites W2015500397 @default.
• W1970794988 cites W2017411996 @default.
• W1970794988 cites W2028749073 @default.
• W1970794988 cites W2044148793 @default.
• W1970794988 cites W2044814201 @default.
• W1970794988 cites W2054458932 @default.
• W1970794988 cites W2066590212 @default.
• W1970794988 cites W2077136462 @default.
• W1970794988 cites W2077510533 @default.
• W1970794988 cites W2080675242 @default.
• W1970794988 cites W2083650072 @default.
• W1970794988 cites W2084274520 @default.
• W1970794988 cites W2092661856 @default.
• W1970794988 cites W2096161283 @default.
• W1970794988 cites W2098938825 @default.
• W1970794988 cites W2105009666 @default.
• W1970794988 cites W2105902511 @default.
• W1970794988 cites W2108158059 @default.
• W1970794988 cites W2112547742 @default.
• W1970794988 cites W2115722806 @default.
• W1970794988 cites W2126867245 @default.
• W1970794988 cites W2131403498 @default.
• W1970794988 cites W2132449659 @default.
• W1970794988 cites W2133016152 @default.
• W1970794988 cites W2141791066 @default.
• W1970794988 cites W2155706932 @default.
• W1970794988 cites W2158333644 @default.
• W1970794988 cites W2158882111 @default.
• W1970794988 cites W2160246216 @default.
• W1970794988 cites W2169949296 @default.
• W1970794988 cites W2187718168 @default.
• W1970794988 cites W2346871664 @default.
• W1970794988 cites W2529334616 @default.
• W1970794988 cites W2099656602 @default.
• W1970794988 doi "https://doi.org/10.1016/j.clpt.2005.08.014" @default.
• W1970794988 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16338276" @default.
• W1970794988 hasPublicationYear "2005" @default.
• W1970794988 type Work @default.
• W1970794988 sameAs 1970794988 @default.
• W1970794988 citedByCount "103" @default.
• W1970794988 countsByYear W19707949882012 @default.
• W1970794988 countsByYear W19707949882013 @default.
• W1970794988 countsByYear W19707949882014 @default.
• W1970794988 countsByYear W19707949882015 @default.
• W1970794988 countsByYear W19707949882016 @default.
• W1970794988 countsByYear W19707949882017 @default.
• W1970794988 countsByYear W19707949882018 @default.
• W1970794988 countsByYear W19707949882019 @default.
• W1970794988 countsByYear W19707949882021 @default.
• W1970794988 countsByYear W19707949882022 @default.
• W1970794988 crossrefType "journal-article" @default.
• W1970794988 hasAuthorship W1970794988A5003784173 @default.
• W1970794988 hasAuthorship W1970794988A5012663330 @default.
• W1970794988 hasAuthorship W1970794988A5022078224 @default.
• W1970794988 hasAuthorship W1970794988A5025109579 @default.
• W1970794988 hasAuthorship W1970794988A5041913194 @default.
• W1970794988 hasAuthorship W1970794988A5045272190 @default.
• W1970794988 hasAuthorship W1970794988A5054318811 @default.
• W1970794988 hasAuthorship W1970794988A5062878299 @default.
• W1970794988 hasAuthorship W1970794988A5080434800 @default.
• W1970794988 hasAuthorship W1970794988A5083433629 @default.
• W1970794988 hasConcept C109650736 @default.
• W1970794988 hasConcept C112705442 @default.
• W1970794988 hasConcept C126322002 @default.
• W1970794988 hasConcept C142462285 @default.
• W1970794988 hasConcept C181389837 @default.
• W1970794988 hasConcept C185592680 @default.
• W1970794988 hasConcept C203014093 @default.
• W1970794988 hasConcept C2522874641 @default.

• next