title: Effect of mycophenolate mofetil on the pharmacokinetics of antiretroviral drugs and on intracellular nucleoside triphosphate pools.
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).
  
  
  METHODS
  Randomised pharmacokinetic study.
  
  
  METHODS
  Nineteen HIV-1-infected patients.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: International Antiviral Therapy Evaluation Center, 1105 AZ Amsterdam, The Netherlands. S.U.Sankatsing@amc.uva.nl
authors.forename: Sanjay U C
authors.initials: SU
authors.lastname: Sankatsing
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Hoggard
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Sparidans
authors.forename: Stephen
authors.initials: S
authors.lastname: Kewn
authors.forename: Kristel M L
authors.initials: KM
authors.lastname: Crommentuyn
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: David J
authors.initials: DJ
authors.lastname: Back
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D003845:Deoxycytosine Nucleotides / Q000493:pharmacokinetics*; D003848:Deoxyguanine Nucleotides / Q000493:pharmacokinetics*; D054306:Dideoxynucleotides; D004347:Drug Interactions; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044966:Anti-Retroviral Agents; D003845:Deoxycytosine Nucleotides; D003848:Deoxyguanine Nucleotides; D054306:Dideoxynucleotides; C417268:lamivudine triphosphate; C024107:2'-deoxycytidine 5'-triphosphate; D019259:Lamivudine; D003570:Cytidine Triphosphate; C029603:deoxyguanosine triphosphate; D009173:Mycophenolic Acid