Session 64Poster Presentations Drug-Drug Interactions Session Day and Time: Wednesday 1:30 - 3:30 pm Room: Hall A
539 Mycophenolate Mofetil Lowers Plasma Nevirapine Concentrations but Has No Effect on Intracellular Triphosphate Concentrations S. Sankatsing*1,2, P. Hoggard3, D. Back3, S. Kewn3, A. Huitema4, K. Crommentuyn4, J. Beijnen4, J. Lange1,2, J. Prins2 1Intl Antiviral Therapy Evaluation Ctr, Amsterdam, The Netherlands; 2Academic Med Ctr, Amsterdam, The Netherlands; 3Univ of Liverpool, UK; and 4Slotervaart Hosp, Amsterdam, The Netherlands
Background: Recent studies suggest a potential role for mycophenolate mofetil (MMF) in the treatment of HIV-1. MMF interferes with cellular guanosine nucleotide biosynthesis, thereby limiting lymphocyte proliferation. This might limit the availability of target cells for HIV-1 infection. In vitro MMF has a direct anti HIV-1 effect and increases the efficacy of abacavir (ABC). Here we studied the effect of MMF on the pharmacokinetic parameters of a number of antiretroviral drugs, and on the intracellular deoxycytidine triphosphate (Dctp) and deoxyguanose triphosphate (Dgtp) pools and triphosphate concentrations of lamivudine (3TCTP) and ABC (CBVTP).
Methods: Fourteen (14) HIV-1 infected, therapy-naïve men started treatment with didanosine 400 mg QD, lamivudine 150 mg BID, abacavir 300 mg BID, indinavir 800 mg BID, ritonavir 100 mg BID, and nevirapine 200 mg BID. They were randomized to a group with or without MMF 500 mg BID. After 8 wks of therapy a plasma pharmacokinetic profile of MMF, abacavir, indinavir and nevirapine, and intracellular triphosphate concentrations in PBMCs were determined. Blood samples were obtained at 0, 2, 4, 6, and 12 h.
Results: Six (6) of the 14 patients (pts) were randomized to receive MMF. There was no difference in plasma AUC and clearance of indinavir or abacavir between the 2 groups. The clearance of nevirapine was 27% higher in pts using MMF (p = 0.018). In 12 pts, of which 5 also received MMF, intracellular triphosphates were measured. There was no significant difference in intracellular Dctp, Dgtp or 3TCTP between the 2 groups at T = 0h (p = 0.149, 0.202, 0.876), T = 2 h (p = 0.537, 0.537, 0.662), T = 6 h (p = 0.432, 0.343, 0.202) and T = 12 h (p = 0.268, 1.000, 0.639). Due to assay interference CBVTP could not be determined.
Conclusion: In this small cohort of pts, MMF reduced the plasma concentration of nevirapine but had no effect on plasma indinavir and abacavir concentrations. In contrast to our hypothesis, there was no consistent effect of MMF on the intracellular concentrations of dCTP, dGTP, or 3TCTP. Additional PK and efficacy data are required to determine the impact of MMF when added to existing antiretroviral therapy.
