Summary
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-, ll-, 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.
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References
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Depré, M., Margolskee, D.J., Van Hecken, A. et al. Dose-dependent kinetics of the enantiomers of MK-571, an LTD4-receptor antagonist. Eur J Clin Pharmacol 43, 431–433 (1992). https://doi.org/10.1007/BF02220622
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DOI: https://doi.org/10.1007/BF02220622