Dose-dependent kinetics of the enantiomers of MK-571, and LTD4-receptor antagonist

Eur J Clin Pharmacol. 1992;43(4):431-3. doi: 10.1007/BF02220622.

Abstract

The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i.v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i.v. doses of MK-571 at weekly intervals. The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, 11-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679. The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Humans
  • Infusions, Intravenous
  • Male
  • Propionates / administration & dosage
  • Propionates / pharmacokinetics*
  • Quinolines / administration & dosage
  • Quinolines / pharmacokinetics*
  • Reference Values
  • SRS-A / antagonists & inhibitors*

Substances

  • Propionates
  • Quinolines
  • SRS-A
  • verlukast