We offer pharmacokinetic (PK), pharmacological (ADME) and safety studies for the lead compounds in early discovery stage.
in vivo study (PK screening)
By administering the lead compound to animals (mouse, rat, rabbit, dog , monkey and more), we can evaluate the basic mechanism of its absorption and main excretion routes.
in vitro study
We offer various in vitro studies in drug discovery stage.
- 1Drug absorption (permeability study using Caco-2 cells)
Caco-2 cells permeability study can be performed to predict human intestinal absorption of the lead compound.
- 2Metabolic stability
Metabolic clearance is predicated by incubating the lead compound in human or animal liver microsomes. The lead compound is then measured by LC-MS/MS to calculate the metabolic activity by measuring the disappearance of the lead compound.
- 3Drug-drug interaction (enzyme inhibition screening)
Drug-drug interaction potential will be evaluated by the effect of the lead compound on probe substances in human liver microsomal P450 expression system.
- 4Protein binding
The binding rate of the lead compound to humans or animal plasma protein is determined using ultrafiltration, equilibrium dialysis or ultracentrifugation method.
Determination of drug concentration in biological samples
We measure the drug concentration in various animal samples (collected from plasma, tissues...etc.) in early discovery stage and report back to the customer in timey manner.
Pharmacological screening study (drug efficacy, secondary pharmacological effect)
We offer various types of package studies to examine profiles of pharmacological effects of a lead compound are available.
in vitro hepatotoxcity evaluation
- 1Bile Acid-Dependent Hepatotoxicity Study
When the lead compound inhibits the transport of the bile salt excretion, the bile salt can be accumulated within the cell which is known to cause the cholestasis. Using the sandwich-cultured primary human hepatocytes, we evaluate the potential of this risk.
- 2Mitochondrial Toxicity Assay
Mitochondrial toxicity is seen in about 80% of the boxed warning compounds reported by the FDA. We can evaluate the toxicity using HepG2 cells and its Crabtree effect.
- 3Reactive Metabolite Identification
- 1Cysteine Trapping Assay
Since some reactive metabolites are unstable, we use 35S cysteine as a trapping reagent to quantify the amount of reactive metabolites.
- 2KCN Trapping Assay
By using K14CN, we can trap and quantify the reactive metabolites cannot be measured by 35S cysteine.
- 3Identification of acylglucuronic conjugates
Acylglucuronic conjugates are highly reactive and also known to contribute to the liver injury. We can evaluate the formation of 1-O-β-glucuronic conjugates to isomers and its rate.
- 4Covalent binding styudy
We can determine the amount of radiolabeled compound and its metabolites that covalently bind to protein using human hepatocytes or liver microsome for in vitro evaluation. For the in vivo evaluation, rats are subjected to the induction of liver metabolic enzymes followed by administration of the radiolabeled compound. The liver is then removed at a specified time and the radioactivity in plasma and the liver will be measured to calculate the covalent binding of the radiolabeled compound.
- 1Cysteine Trapping Assay