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01.10.2004 | Original Research Article

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

verfasst von: Dr Sanjay U. C. Sankatsing, Patrick G. Hoggard, Alwin D. R. Huitema, Rolf W. Sparidans, Stephen Kewn, Kristel M. L. Crommentuyn, Joep M. A. Lange, Jos H. Beijnen, David J. Back, Jan M. Prins

Erschienen in: Clinical Pharmacokinetics | Ausgabe 12/2004

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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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Titel: Effect of Mycophenolate Mofetil on the Pharmacokinetics of Antiretroviral Drugs and on Intracellular Nucleoside Triphosphate Pools
verfasst von: Dr Sanjay U. C. Sankatsing
Patrick G. Hoggard
Alwin D. R. Huitema
Rolf W. Sparidans
Stephen Kewn
Kristel M. L. Crommentuyn
Joep M. A. Lange
Jos H. Beijnen
David J. Back
Jan M. Prins
Publikationsdatum: 01.10.2004
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 12/2004
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200443120-00004