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Effect of Mycophenolate Mofetil on the Pharmacokinetics of Antiretroviral Drugs and on Intracellular Nucleoside Triphosphate Pools

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Abstract

Objective

To study the effect of mycophenolate mofetil therapy on the pharmacokinetic parameters of a number of antiretroviral drugs, on intracellular pools of deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP), and on intracellular concentrations of the triphosphate of lamivudine (3TCTP).

Design

Randomised pharmacokinetic study.

Participants

Nineteen HIV-1-infected patients.

Methods

Antiretroviral-naive men starting treatment with didanosine 400mg once daily, lamivudine 150mg twice daily, abacavir 300mg twice daily, indinavir 800mg twice daily, ritonavir 100mg twice daily and nevirapine 200mg twice daily were randomised to a group with or without mycophenolate mofetil 500mg twice daily. After 8 weeks of therapy, the plasma pharmacokinetic profiles of mycophenolic acid (the active metabolite of mycophenolate mofetil), abacavir, indinavir and nevirapine, and triphosphate concentrations (dCTP, dGTP and 3TCTP) in peripheral blood mononuclear cells, were determined.

Results

Nine of the 19 patients received mycophenolate mofetil. There was no difference in plasma clearance of indinavir or abacavir between the two groups. The clearance of nevirapine was higher in patients using mycophenolate mofetil (p = 0.04). In 12 patients, of whom five also received mycophenolate mofetil, intracellular triphosphates were measured. There was no significant difference in intracellular dCTP, dGTP or 3TCTP concentrations between the two groups. Conclusion: In this small cohort of patients, mycophenolate mofetil therapy reduced the plasma concentration of nevirapine but had no effect on plasma concentrations of indinavir and abacavir. There were no consistent effects of mycophenolic acid on the intracellular concentrations of dCTP, dGTP or 3TCTP.

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Acknowledgements

We thank Marijke Roos, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, The Netherlands, for measuring lymphocyte proliferation. This study was financially supported by a private foundation that wishes not to be named.

Part of this study was presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA, USA in February 2003.

The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. International Antiviral Therapy Evaluation Center, Meibergdreef 9, Room T0-111, 1105 AZ, Amsterdam, The Netherlands

    Sanjay U. C. Sankatsing & Joep M. A. Lange

  2. Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Sanjay U. C. Sankatsing, Joep M. A. Lange & Jan M. Prins

  3. Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK

    Patrick G. Hoggard, Stephen Kewn & David J. Back

  4. Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands

    Alwin D. R. Huitema, Kristel M. L. Crommentuyn & Jos H. Beijnen

  5. Department of Drug Toxicology, Utrecht University, Utrecht, The Netherlands

    Rolf W. Sparidans & Jos H. Beijnen

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  1. Sanjay U. C. Sankatsing
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  2. Patrick G. Hoggard
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Correspondence to Sanjay U. C. Sankatsing.

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Sankatsing, S.U.C., Hoggard, P.G., Huitema, A.D.R. et al. Effect of Mycophenolate Mofetil on the Pharmacokinetics of Antiretroviral Drugs and on Intracellular Nucleoside Triphosphate Pools. Clin Pharmacokinet 43, 823–832 (2004). https://doi.org/10.2165/00003088-200443120-00004

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