Authors: Sankatsing, Sanjay U.C.; Hoggard, Patrick G.¹; Huitema, Alwin D.R.²; Sparidans, Rolf W.³; Kewn, Stephen¹; Crommentuyn, Kristel M.L.²; Lange, Joep M.A.; Beijnen, Jos H.; Back, David J.¹; Prins, Jan M.⁴

Source: Clinical Pharmacokinetics, Volume 43, Number 12, 2004 , pp. 823-832(10)

Publisher: Adis International

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.

Keywords: Abacavir, drug interactions; Abacavir, pharmacokinetics; Antiretrovirals, drug interactions; Antiretrovirals, pharmacokinetics; Drug interactions; HIV 1 infections; Immunosuppressants, drug interactions; Immunosuppressants, pharmacokinetics; Indinavir, drug interactions; Indinavir, pharmacokinetics; Mycophenolate mofetil, drug interactions; Mycophenolate mofetil, pharmacokinetics; Nevirapine, drug interactions; Nevirapine, pharmacokinetics

Document Type: Research article

Affiliations: 1: 3 Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK 2: 4 Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands 3: 5 Department of Drug Toxicology, Utrecht University, Utrecht, The Netherlands 4: 2 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Publication date: 2004-01-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Sankatsing, Sanjay U.C. ;  Hoggard, Patrick G. ;  Huitema, Alwin D.R. ;  Sparidans, Rolf W. ;  Kewn, Stephen ;  Crommentuyn, Kristel M.L. ;  Lange, Joep M.A. ;  Beijnen, Jos H. ;  Back, David J. ;  Prins, Jan M.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers