Best Single Time Point Correlations with AUC for Cyclosporine and Tacrolimus in HIV-Infected Kidney and Liver Transplant Recipients
Year of Publication
Frasetto, LA; Tan-Tam, CC; Barin, B; Browne, M; Wolfe, AR; Stock, PG; Roland, M; Benet, LZ
Antiretrovirals; Drug interactions; HIV; Immunosuppressants; Pharmacokinetics
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.