In vivo & in vitro ADME

In vivo ADME assay (small molecule drug)

A
Absorption

Pharmacokinetic studies of single and repeated doses / PK bridging studies / Formulation screening

Species: mice , rats , rabbits , dogs , monkeys, etc.

Routes of administrations: Intravenous / Subcutaneous / Transdermal / Intramuscular / Intraperitoneal / Oral / Sublingual / Nasal, etc.

Detection matrix type: Plasma / Whole Blood

Detection method : LC-MS/MS

Detection indicators: T_max、C_max、AUC_last/AUC_inf、t_1/2、Vss、CL

D
Distribution

Tissue distribution studies / brain-blood ratio studies

Species: mice , rats , rabbits , dogs , monkeys, etc.

Routes of administrations: Intravenous / Subcutaneous / Transdermal / Intramuscular / Intraperitoneal / Oral / Sublingual / Nasal, etc.

Detection matrix type: Plasma / Whole blood/heart, liver, spleen, lung, kidney, brain, gastrointestinal tract, bone marrow, skeletal muscle, skin, and other tissues.

Detection method : LC-MS/MS

Detection indicators: T_max、C_max、AUC_last、tissue to plasma concentration ratio, etc.

M
Metabolism

In vivo metabolite studies

Species: mice , rats , rabbits , dogs , monkeys, etc.

Routes of administrations: Intravenous / Subcutaneous / Transdermal / Intramuscular / Intraperitoneal / Oral / Sublingual / Nasal, etc.

Detection matrix types: plasma / whole blood, urine / feces / bile (rat), cerebrospinal fluid (monkey)

E
Excretion

Excretion studies / Material balance

Species: mice , rats , rabbits , dogs , monkeys, etc.

Routes of administration: intravenous / subcutaneous / intramuscular / intraperitoneal / oral, etc.

Detection substrate types: urine / feces / bile

Detection method: LC-MS/MS method

Detection indicators: excretion rate, cumulative excretion volume, cumulative excretion rate, etc.

In vivo ADME Application Studies

Routes of administration: intravenous / subcutaneous / transdermal / intramuscular / intraperitoneal / oral / sublingual / nasal / intrathecal injection, etc.

Absorption

In vivo pharmacokinetic studies

Species: mice, rats, dogs, and cynomolgus monkeys.

Studies type: Single-dose pharmacokinetic (PK) studies/
Repeated-dose PK studies/
Equivalence studies / PK bridging studies

Distribution

Tissue distribution assay

Species: mice, rats. etc.

Studies type: tissue distribution test for single-dose / repeated-dose administration, brain-blood ratio test (Kp,uu)

Metabolism

Identification of in vivo metabolites

Species: mice, rats. dogs , and cynomolgus monkeys

Identification study of metabolites in plasma / urine / feces / bile / tissue after repeated administration.

Excretion

Fecal / urine / bile excretion

Species: rats

After a single dose, feces / urine / bile were collected to determine the excretion volume / recovery rate / excretion rate.

Method validation

LC-MS/MS

Develop and establish : LC-MS/MS bioanalytical methods and conduct systematic method validation.

Matrix types: plasma / whole blood / cerebrospinal fluid / urine / feces / bile / tissue

In vitro ADME assay (small molecule drugs)

Absorption

Permeability test and P-gp /BCRP drug transport assay /SLC transporter drug uptake assay

Osmosis and transmembrane transport models

Caco-2 cell line (P-gp /BCRP)
MDCK-MDR1 cells (P-gp)
Transfected HEK-293 cells ( OATP1B1 , OATP1B3 , OAT1 , OAT3 , OCT2 , MATE1 , MATE2-K ).

Distribution

Plasma / tissue protein binding and whole blood - plasma partition ratio test

Matrix materials for analysis: plasma, whole blood, liver microsomes, rodent tissue homogenates (brain tissue / liver tissue / kidney tissue / bone marrow tissue, etc.)

Species examined: mouse, rat, beagle, Bama pig, cynomolgus monkey, human

Metabolism

In vitro metabolic stability study

Test substrates: plasma / whole blood, liver microsomes / liver S9 cells/hepatocytes / liver lysosomes, artificial gastrointestinal fluid, etc.

Species examined: mouse, rat, beagle, cynomolgus monkey, and human (excluding artificial gastrointestinal fluid).

Metabolism

Investigation of CYP enzyme inhibition and induction capabilities

Metabolic enzyme inhibition: CYP1A2 , CYP2B6 , CYP2C8 , CYP2C9 , CYP2C19 , CYP2D6 and CYP3A ( IC50 and TDI )

Metabolic enzyme induction: CYP1A2 , CYP2B6 , and CYP3A4 , etc.

Metabolism

Enzyme Phenotyping Studies

Metabolic enzymes: CYP1A2 , CYP2B6 , CYP2C8 , CYP2C9 , CYP2C19 , CYP2D6 , and CYP3A ; UGT ; chemical inhibition or recombinant enzyme method.

Metabolism

Metabolite Identification Studies

Specimen composition: plasma, liver microsomes / liver S9/ hepatocytes / liver lysosomes, artificial gastrointestinal fluid

Species examined: mouse, rat, beagle, cynomolgus monkey, human

In vitro ADME application trial

In vitro pharmacokinetic
&
Drug interaction assessment studies

Support IND registration
applications for new drugs / excipients

01 Plasma metabolic stability (mice, rats, beagles, cynomolgus monkeys, humans)

02 Plasma protein binding (mice, rats, beagles, cynomolgus monkeys, humans)

03 Whole blood plasma partition ratio (mice, rats, beagles, cynomolgus monkeys, humans)

04 Hepatic microsomal / hepatocyte / hepatic S9 metabolic stability (mice, rats, beagles, cynomolgus monkeys, humans)

05 Identification and species differences of liver microsomes / hepatocytes / liver S9 metabolites (mice, rats, beagles, cynomolgus monkeys, humans)

06 CYPs enzyme phenotype study of test substances (chemical inhibition method and human recombinant enzyme method)

07 Study on the inhibition of CYPs by the test substance (inhibition and time-dependent inhibition)

08 Study on the induction of CYPs by the test substance

09 Caco-2 permeability and ABC (P-gp /BCRP) substrate studies

10 Inhibition study of the test substance on the ABC (P-gp /BCRP) transporter

11 SLC transporter substrate study

12 Inhibition study of the test substance on SLC transporters