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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 12/2004

01-10-2004 | Original Research Article

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

Authors: 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

Published in: Clinical Pharmacokinetics | Issue 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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Metadata
Title
Effect of Mycophenolate Mofetil on the Pharmacokinetics of Antiretroviral Drugs and on Intracellular Nucleoside Triphosphate Pools
Authors
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
Publication date
01-10-2004
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 12/2004
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200443120-00004