Contribution of a significant first-pass effect of dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate in the liver to its poor bioavailability in rats

Abstract

These observations indicated that despite the fact that DDB was readily permeable to the intestinal epithelium, a significant first-pass metabolism was associated with its pharmacokinetics in rats.

Kinetics of the Absorption, Distribution, Metabolism, and Excretion of Lobeglitazone, a Novel Activator of Peroxisome Proliferator-Activated Receptor Gamma in Rats

“…Assuming the mechanism of interaction between LB and digoxin is competitive, the Ki would be regarded as reflecting the affinity of the LB for the transporter (i.e., MDR1). The intestinal fluid in 250 g rat is approximately 2.5 mL, 18 and the concentration of LB in the intestine would be expected to be approximately 104 and 416 :M for 0.5 and 2 mg/kg oral administration, respectively [i.e., molecular weight (LB) of 480.2 g/mol]. The expected concentration would be significantly greater than the estimated affinity of LB (i.e., 12.5 :M) so that MDR1-mediated transport is saturated in our oral administration study.…”