Pharmacokinetics of mycophenolic acid in severe lupus nephritis

Kidney Int. 2010 Aug;78(4):389-95. doi: 10.1038/ki.2010.170. Epub 2010 Jun 9.

Abstract

Mycophenolic acid (MPA) is an effective treatment for active lupus nephritis despite its variable efficacy in different ethnic groups. Here we tested whether pharmacokinetic monitoring may help to optimize dosing of MPA in an Asian population. Patients with biopsy-proven class III or IV lupus nephritis (ISN/RPS category) were treated with mycophenolate mofetil or enteric-coated mycophenolate sodium. One month after initiating treatment we measured plasma MPA levels in eight samples taken over a 12-h period after drug administration. The mean area under the time-dependent curve for MPA of responding patients was significantly higher than those not responding. Successful treatment was seen in patients with areas >45 mg h/l. The dosage of the drug was not related to MPA pharmacokinetics. In the mycophenolate mofetil group, however, MPA-area under the curve was positively, and significantly, correlated with trough or 1 h after dose concentrations and associated with a therapeutic response. Thus, our study shows that MPA pharmacokinetics were positively correlated with therapeutic responses of mycophenolate, suggesting that controlling the concentrations may improve its therapeutic efficacy in lupus nephritis. As the absorption and pharmacokinetic peak of enteric-coated tablets is slower, it is important to take different formulations into account when determining optimal MPA concentrations.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Adult
  • Area Under Curve
  • Asian People
  • Drug Monitoring
  • Female
  • Humans
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / ethnology
  • Male
  • Mycophenolic Acid / administration & dosage*
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacokinetics*
  • Pharmacokinetics
  • Tablets, Enteric-Coated / administration & dosage
  • Tablets, Enteric-Coated / pharmacokinetics

Substances

  • Tablets, Enteric-Coated
  • Mycophenolic Acid