Kinetics of the Absorption, Distribution, Metabolism, and Excretion of Lobeglitazone, a Novel Activator of Peroxisome Proliferator-Activated Receptor Gamma in Rats.
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Lee JH, Noh CK, Yim CS, Jeong YS, Ahn SH, Lee W, Kim DD, Chung SJ
Kinetics of the Absorption, Distribution, Metabolism, and Excretion of Lobeglitazone, a Novel Activator of Peroxisome Proliferator-Activated Receptor Gamma in Rats.
J Pharm Sci. 2015 Sep;104(9):3049-59. doi: 10.1002/jps.24378. Epub 2015 Feb 3.
- PubMed ID
- 25648999 [ View in PubMed]
- Abstract
This study was performed to determine biopharmaceutical properties of lobeglitazone (LB), a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, in rats. In parallel artificial membrane permeability assay and Madin-Darby canine kidney (MDCK) cell permeability assays of LB, the activator was found to interact with multidrug-resistance protein 1 (MDR1) and OATP1B1. The concentration resulting in 50% inhibition value for LB in MDR1 expressing MDCK cells was approximately 12.5 +/- 3.61 muM. LB had adequate stability (i.e., 56% remaining at 0.5 h) in rat liver microsomes. A cytochrome P450 (CYP) inhibitory potency study indicated that LB is primarily interacted with CYP1A2, 2C9, and 2C19. In rats, LB appeared to be readily absorbed after an oral administration (an absolute bioavailability of approximately 95%). Following intravenous administration, LB exhibited linear pharmacokinetics in the dose range of 0.5-2 mg/kg. The primary distribution site was the liver but it was also distributed to heart, lungs, and fat tissue. The excretion of LB to the urine, bile, feces, and intestine was insignificant (i.e., <10% of the dose) in rats. These observations suggest that, despite the fact that it interacts with some drug transporters and metabolizing enzymes, the pharmacokinetics of LB were linear with a high oral bioavailability.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Lobeglitazone Peroxisome proliferator-activated receptor gamma Protein Humans YesActivatorDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Lobeglitazone Cytochrome P450 1A2 Protein Humans NoInhibitorDetails Lobeglitazone Cytochrome P450 2C19 Protein Humans NoInhibitorDetails Lobeglitazone Cytochrome P450 2C9 Protein Humans NoInhibitorDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Lobeglitazone P-glycoprotein 1 Protein Humans NoNot Available Details Lobeglitazone Solute carrier organic anion transporter family member 1B1 Protein Humans NoInhibitorDetails Lobeglitazone Solute carrier organic anion transporter family member 3A1 Protein Humans NoInhibitorDetails