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, and the concentration of LB in the intestine would be expected to be approximately 104 and 416 μM 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 μM) so that MDR1‐mediated transport is saturated in our oral administration study.…”

Pharmacokinetic-Pharmacodynamic Analysis on Inflammation Rat Model after Oral Administration of Huang Lian Jie Du Decoction

“…Many oral drugs are metabolized in the digestive tract and liver before they travel to the target organs [ 54 ]. The low bioavailability of oral drugs is due to intestinal bioconversion [ 55 ] or the liver and intestinal first-pass effect [ 40 , 56 – 58 ]. The HCR and pharmacokinetic behaviors of the main ingredients in HLJDD provide beneficial guidance for its clinical use.…”