title: Best single time point correlations with AUC for cyclosporine and tacrolimus in HIV-infected kidney and liver transplant recipients.
abstract: BACKGROUND
  Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, tacrolimus (TAC) trough levels (C0) or cyclosporine (CsA) drawn at C0 or 2 hours after dosing (C2) correlate with drug exposure (area under the curve [AUC]/dose) and outcomes. Because of ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, this study investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels.
  
  
  METHODS
  This study prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS in 150 studies over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with liquid chromatography-tandem mass spectrometry and AUC calculated using WinNonlin 9.0. Correlation analyses were run on SAS 9.2.
  
  
  RESULTS
  CsA concentration at C4 correlated better with AUC than C0 or C2, and over time TAC concentration correlated better at C0 or C2.
  
  
  CONCLUSIONS
  It is suggested that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.
authors.affiliation: 1 Department of Medicine and Clinical Research Center, University of California, San Francisco, CA. 2 Department of Surgery, University of California, San Francisco, CA. 3 EMMES, Bethesda, MD. 4 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA. 5 Address correspondence to: Leslie Z. Benet, Ph.D., UCSF Box 0912, San Francisco, CA 94143-0912.
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Frassetto
authors.forename: Clara C
authors.initials: CC
authors.lastname: Tan-Tam
authors.forename: Burc
authors.initials: B
authors.lastname: Barin
authors.forename: Matt
authors.initials: M
authors.lastname: Browne
authors.forename: Alan R
authors.initials: AR
authors.lastname: Wolfe
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stock
authors.forename: Michelle
authors.initials: M
authors.lastname: Roland
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D002853:Chromatography, Liquid; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000009:adverse effects; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus