title: Pharmacokinetics of abacavir and its anabolite carbovir triphosphate without and with darunavir/ritonavir or raltegravir in HIV-infected subjects.
abstract: BACKGROUND
  Here, we aimed to investigate the pharmacokinetics of abacavir and carbovir triphosphate (CBV-TP) with darunavir/ritonavir 900/100 mg once daily or raltegravir 400 mg twice daily.
  
  
  METHODS
  HIV-infected subjects on abacavir (600 mg once daily) underwent steady-state pharmacokinetic assessments without and with darunavir/ritonavir or raltegravir. Within-subject changes in plasma and intracellular pharmacokinetic parameters were evaluated by geometric mean ratios (GMRs) and 90% CIs.
  
  
  RESULTS
  A total of 19 patients completed the study. With darunavir/ritonavir (versus abacavir alone), abacavir GMRs (90% CI) were 0.73 (0.66, 0.80), 0.62 (0.50, 0.77) and 0.78 (0.69, 0.87) for area under the curve (AUC), trough concentration (C(trough)) and maximum concentration (C(max)), respectively. With raltegravir, they were 1.03 (0.97, 1.10), 0.83 (0.62, 1.11) and 1.06 (0.95, 1.18), respectively. Intracellular CBV-TP GMRs (90% CI) were 0.88 (0.72, 1.07), 0.68 (0.48, 0.95) and 0.98 (0.79, 1.23) for AUC, C(trough) and C(max), respectively, with darunavir/ritonavir, and 0.96 (0.76, 1.20), 0.57 (0.33, 1.00) and 1.07 (0.85, 1.35), respectively, with raltegravir.
  
  
  CONCLUSIONS
  There was a 27% decrease in abacavir plasma exposure with darunavir/ritonavir and no changes with raltegravir. CBV-TP C(trough) was significantly decreased with darunavir/ritonavir (32%) and showed a high inter-individual variability with raltegravir.
authors.affiliation: St Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Laura
authors.initials: L
authors.lastname: Dickinson
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: Jessica
authors.initials: J
authors.lastname: Taylor
authors.forename: Keerti
authors.initials: K
authors.lastname: Gedela
authors.forename: George
authors.initials: G
authors.lastname: Abongomera
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D018592:Cross-Over Studies; D000069454:Darunavir; D003848:Deoxyguanine Nucleotides / Q000097:blood / Q000493:pharmacokinetics*; D015224:Dideoxynucleosides / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000097:blood / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000032:analysis; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics*; D019562:Viral Load / Q000187:drug effects; D000099227:Abacavir; D006160:Guanosine Triphosphate
chemical_list: D019380:Anti-HIV Agents; D000069454:Darunavir; D003848:Deoxyguanine Nucleotides; D015224:Dideoxynucleosides; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D019438:Ritonavir; D013449:Sulfonamides; D000099227:Abacavir; C066928:carbovir triphosphate; D006160:Guanosine Triphosphate