The influence of norfloxacin and metronidazole on the disposition of mycophenolate mofetil.

Published

Journal Article

The objective of this study was to investigate the effect of concurrent antibiotic administration on the disposition of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) after oral administration of mycophenolate mofetil (MMF) in healthy subjects. Eleven healthy subjects were enrolled. The study was divided into 4 treatment periods. Subjects received MMF as a single oral 1-g dose alone and were then randomized to 3 antibiotic treatment periods. The 3 periods included norfloxacin, metronidazole, and a combination of norfloxacin and metronidazole. Antibiotic treatment was started 3 days prior to each MMF pharmacokinetic study day and was given for a total of 5 days. On day 4 of each antibiotic phase, subjects received a single 1-g oral dose of MMF. Plasma and urine samples were obtained over 48 hours after the MMF dose in all treatment periods and were quantitatively measured for MPA and MPAG. Pharmacokinetic parameters for MPA and MPAG were determined for all periods. Compared to MMF alone, the area under the plasma concentration versus time curve (AUC) of MPA was reduced by an average of 10%, 19%, and 33% when given with norfloxacin, metronidazole, and norfloxacin plus metronidazole, respectively. The AUC of MPAG was also reduced on average by 10%, 27%, and 41% in the corresponding periods. The combination of norfloxacin and metronidazole significantly reduced the AUC of MPA and MPAG in healthy subjects. This likely occurs as a result of reduced enterohepatic recirculation.

Full Text

Cited Authors

  • Naderer, OJ; Dupuis, RE; Heinzen, EL; Wiwattanawongsa, K; Johnson, MW; Smith, PC

Published Date

  • February 2005

Published In

Volume / Issue

  • 45 / 2

Start / End Page

  • 219 - 226

PubMed ID

  • 15647415

Pubmed Central ID

  • 15647415

Electronic International Standard Serial Number (EISSN)

  • 1552-4604

International Standard Serial Number (ISSN)

  • 0091-2700

Digital Object Identifier (DOI)

  • 10.1177/0091270004271555

Language

  • eng