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Session 64 Poster Presentations Drug-Drug Interactions Session Day and Time: Wednesday 1:30 - 3:30 pm Room: Hall A

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Pharmacokinetics and Pharmacodynamics of Low-dose Mycophenolate Mofetil in Early Stage HIV-infected Patients Successfully Treated with HAART
J. Martorell¹, M. Brunet¹, F. García¹, G. Mestre*¹, M. Plana¹, A. Libois¹, T. Gallart¹, T. Pumarola¹, J. Miró¹, J. L. Blanco¹, E. Martínez¹, J. Mallolas¹, J. Lange², G. Pantaleo³, J. M Gatell^1
1Inst d'Investigacions Biomèdiques August Pi i Sunyer, Hosp Clin, Univ of Barcelona, Spain; ²Intl Antiviral Therapy Eval Ctr, Amsterdam, The Netherlands; and ³Lab of AIDS Immunopathogenesis, Hosp de Baeumont Lausanne, Switzerland

Background: Mycophenolate mofetil, has been proposed to potentiate the inhibition of human immunodeficiency virus (HIV) replication mediated by some antiretroviral agents. We compare pharmacokinetic and pharmacodynamic of two doses 0.25 g BID and 0.5 g BID.
Methods: MPA plasma levels (HPLC), and the capacity of patient sera to inhibit CEM cell line proliferation (H3Thymidine uptake), were measured post dose at 0, 20, 40 min and1, 2, 4, 6, 8, 10, 12 hr in early stage HIV infected patients (pts) successfully treated with HAART and mycophenolate mofetil, at wks 0, 3, and 20 of treatment onset in 2 trials (MMF trial, n = 9, doses 0.25 g BID; MOCHA, n = 8 doses 0.5 g BID). The control group were 9 pts treated with HAART without mycophenolate.
Results: The PK profiles of MPA was similar at wks 3 and 20. Overall results in 0.25 g BID group were: Cmin 0.60 (0.20-4.67) mg/L; AUC 15.3 (10.4-24.4) mg*hr/L; Cmax 2.60 (0.94-7.98) mg/L; in 0.5 g BID group were: Cmin 0.68 (0.34-2.53) mg/L; AUC 17.15 (12.5-21.87) mg*hr/L; Cmax 6.59 (2.14-12.02) mg/L. Pt sera pre-treatment onset does not inhibit CEM proliferation 98.2 (92.6-100.0). Post-treatment pt sera inhibited CEM proliferation to < 40 % in 0.25g BID group at 0 hr 71%; 1 hr 97%; 2 hr 91%; 4 hr 63%; and 12 hr 23% of curves; and in 0.5g BID group at 0 hr 38%; 1 hr 93%; 2 hr 85%; 4 hr 46%; and 12 hr 0% of curves.
Conclusions: Sera from the majority of pts receiving low doses of mycophenolate mofetil (0.25g or 0.5 g BID) inhibit lymphocyte proliferation during most of the interdose intervals despite low MPA plasma levels. For some pts higher doses could be necessary, the capacity of sera to inhibit CEM proliferation can help to identify those pts. Cmax is the only parameter higher in 0.5 g BID vs 0.25 mg BID, while the AUC, Cmin or inhibition of lymphocyte proliferation were similar in both groups.

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