Effect of mycophenolate mofetil on the pharmacokinetics of antiretroviral drugs and on intracellular nucleoside triphosphate pools

• Published in: Clinical pharmacokinetics 2004-01, Vol.43 (12), p.823-832
• Main Authors: SANKATSING, Sanjay U. C, HAGGARD, 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
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - metabolism; Adult; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Anti-Retroviral Agents - pharmacokinetics; Anti-Retroviral Agents - therapeutic use; Biological and medical sciences; Cytidine Triphosphate - analogs & derivatives; Cytidine Triphosphate - pharmacokinetics; Deoxycytosine Nucleotides - pharmacokinetics; Deoxyguanine Nucleotides - pharmacokinetics; Dideoxynucleotides; Drug Interactions; HIV-1; Humans; Immunomodulators; Lamivudine - analogs & derivatives; Lamivudine - pharmacokinetics; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - blood; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; Pharmacology. Drug treatments
• ISSN: 0312-5963; 1179-1926
• DOI: 10.2165/00003088-200443120-00004

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). Randomised pharmacokinetic study. Nineteen HIV-1-infected patients. Antiretroviral-naive men starting treatment with didanosine 400 mg once daily, lamivudine 150 mg twice daily, abacavir 300 mg twice daily, indinavir 800 mg twice daily, ritonavir 100 mg twice daily and nevirapine 200 mg twice daily were randomised to a group with or without mycophenolate mofetil 500 mg 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. 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. 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.