Comparative in vitro metabolism of phospho-tyrosol-indomethacin by mice, rats and humans

The anticancer effect of phospho-tyrosol-indomethacin (MPI-621), a novel phosphoderivative of indomethacin: in vitro and in vivo studies.

We have synthesized a novel derivative of indomethacin, phospho-tyrosol-indomethacin (PTI; MPI-621), and evaluated its anticancer efficacy in vitro and in vivo. PTI inhibited the growth of human colon, breast and lung cancer cell lines 6-30-fold more potently than indomethacin. In vivo, in contrast to indomethacin that was unable to inhibit colon cancer xenograft growth, PTI inhibited the growt...

Comparative Metabolism of C-14-labeled Apixaban in Mice, Rats, Rabbits, Dogs, and Humans

Comparative metabolism of 14C-labeled apixaban in mice, rats, rabbits, dogs, and humans.

The metabolism and disposition of [(14)C]apixaban, a potent, reversible, and direct inhibitor of coagulation factor Xa, were investigated in mice, rats, rabbits, dogs, and humans after a single oral administration and in incubations with hepatocytes. In plasma, the parent compound was the major circulating component in mice, rats, dogs, and humans. O-Demethyl apixaban sulfate (M1) represented a...

Comparative Metabolism of C-Labeled Apixaban in Mice, Rats, Rabbits, Dogs, and Humans

The metabolism and disposition of [C]apixaban, a potent, reversible, and direct inhibitor of coagulation factor Xa, were investigated in mice, rats, rabbits, dogs, and humans after a single oral administration and in incubations with hepatocytes. In plasma, the parent compound was the major circulating component in mice, rats, dogs, and humans. O-Demethyl apixaban sulfate (M1) represented appro...

Metabolism of intravenous methylnaltrexone in mice, rats, dogs, and humans.

Methylnaltrexone (MNTX), a selective mu-opioid receptor antagonist, functions as a peripherally acting receptor antagonist in tissues of the gastrointestinal tract. This report describes the metabolic fate of [(3)H]MNTX or [(14)C]MNTX bromide in mice, rats, dogs, and humans after intravenous administration. Separation and identification of plasma and urinary MNTX metabolites was achieved by hig...