Dose-dependent kinetics of the enantiomers of MK-571, and LTD4-receptor antagonist.
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.
Depré
M
M
Department of Pharmacology, School of Medicine, University of Leuven, Belgium.
Margolskee
D J
DJ
Van Hecken
A
A
Hsieh
J S
JS
Buntinx
A
A
De Schepper
P J
PJ
Rogers
J D
JD
D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011422:Propionates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values; D013189:SRS-A / Q000037:antagonists & inhibitors*
D011422:Propionates; D011804:Quinolines; D013189:SRS-A; C059141:verlukast