Metabolic fate of sipoglitazar, a novel oral PPAR agonist with activities for PPAR-γ, -α and -δ, in rats and monkeys and comparison with humans in vitro.

Sipoglitazar is a novel anti-diabetic agent with triple agonistic activities on the human peroxisome proliferator-activated receptors, hPPAR-γ, -α, and -δ. The bioavailability for sipoglitazar was 95.0% and 72.

Marked impact of P-glycoprotein on the absorption of TAK-427 in rats.

The role of P-glycoprotein (P-gp, ABCB1) on the absorption process was investigated by drug-drug interaction studies of TAK-427 with P-gp inhibitors (erythromycin, ketoconazole or quinidine) in rats and by transport studies using rat multidrug resistance (MDR1) stably expressing cells and rat small intestine mounted in a Ussing-type chamber. TAK-427 showed high efflux activity with low permeability in rat MDR1a and MDR1b stably expressing cells and was revealed to be a typical substrate for P-gps. Although TAK-427 was mainly absorbed from the small intestine in rats, a large part of the dosed compound remained in the gastrointestinal tract.

Pharmacokinetic interaction between TAK-044, a new endothelin antagonist, and ciclosporin in rats.

The pharmacokinetic interaction between TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-alanyl-L- alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium, CAS 157380-72-8) and ciclosporin (CAS 59865-13-3) was investigated after concomitant intravenous (i.v.) administration in rats.

Disposition of TAK-044, a new endothelin antagonist, in rats and dogs.

The disposition of TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-alanyl-L- alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl] disodium, CAS 157380-72-8), a new endothelin antagonist, was studied in rats and dogs by using 14C-labeled drug ([14C]TAK-044). After a single intravenous administration of [14C]TAK-044 at 3 mg/kg to rats and dogs, the concentrations of TAK-044 in plasma declined biphasically; t1/2 alpha and t1/2 beta were 0.03 and 1.