Mediford Corporation offers an extensive menu of in vivo and in vitro pharmacokinetic testing services that are conducted in accordance with Standards of Reliability of Application Data (Pharmaceuticals and Medical Devices Act), OECD GLP and GLP for agricultural chemicals under an operational management system that has been confirmed as GLP-compliant through inspections by domestic and foreign regulatory authorities on safety studies of pharmaceuticals and agricultural chemicals. In particular, our skin permeability studies in accordance with GLP for agricultural chemicals have been well received as one of our frontline services.

We continue to satisfy the diverse needs in various aspects of our clients’ research and development projects while keeping an eye on the latest technologies, various guidelines, and regulation trends. Please contact us with any inquiries or requests.

Service details

Pharmacokinetic Studies

ADME studies (Absorption, Distribution, Metabolism, Excretion)

We conduct pharmacokinetic studies (absorption, distribution, metabolism, and excretion studies using various types of animals) in compliance with Standards of Reliability of Application Data (Pharmaceuticals and Medical Devices Act), GLP for agricultural chemicals, and OECD GLP at GLP-compliant facilities that have obtained AAALAC accreditation. Measurement data are collected and calculated online by a validated pharmacokinetic study support system to ensure Data Integrity.

Placental/Fetal transfer, milk secretion

We measure tissue radioactivity levels in pregnant rats (during organogenesis and perinatal period).
Tissue excision and QWBA methods are available for evaluation.
We also measure the radioactivity concentration in milk and plasma of lactating rats over time to evaluate the transfer of the test substance into milk.

Pharmacokinetic study using human liver chimeric mice

We measure and analyze metabolites in biological samples by administering test substances to mice transplanted with normal human hepatocytes (human liver chimeric mice). We help reduce risks in drug development by confirming the presence of human-specific metabolite formation in vivo at an early stage.

We can also conduct pharmacokinetic studies using various pathological models based on the technologies for creating pathological models that we have built up in the course of conducting contract pharmacology studies. Please contact us for more information on applicable pathological models.

Plasma protein binding

We evaluate the protein binding rate of the test substance in vitro. In vivo evaluation is also possible in experimental animals.

Evaluation animals
Humans, monkeys, dogs, rabbits, rats, mice, etc.
Sample
Plasma, serum, and purified protein (albumin, α1-acid glycoprotein, γ-globulin, etc.)
Evaluation method
Ultrafiltration, ultracentrifugation, and equilibrium dialysis
Evaluation items
Protein binding rate, identification of bound proteins, etc.

Blood cell distribution

We evaluate the blood cell distribution of the test substance in vitro. In vivo evaluation can also be performed on experimental animals.

Evaluation animals
Humans, monkeys, dogs, rabbits, rats, mice, etc.
Sample
Fresh blood
Evaluation items:
Blood cell distribution (%), and blood/plasma concentration ratio (Rb)

Drug-metabolizing enzyme inhibition

We evaluate the effect of the test substance on drug metabolizing enzymes in vitro using human liver microsomes.

Enzyme source
Human liver microsomes
Measurement method
LC/MS/MS
Enzymes evaluated
CYP, UGT, etc.
Evaluation items
Drug interactions related to metabolic inhibition

Drug-metabolizing enzyme and isoform identification

We evaluate the enzymes and isoforms involved in the metabolism of the test substance in vitro using cell fractions prepared from human liver and expression systems for each drug-metabolizing enzyme.

Identification of drug metabolizing enzymes
Enzymes evaluated
CYP, UGT, FMO, GST, etc.
Enzyme sources
Human liver microsomes, human liver cytosol, human liver S9, various expressing enzymes (CYP, FMO, UGT)
Evaluation items
Cofactor requirement (CYP, FMO, UGT, ST, GST), metabolism by expressing enzymes (CYP, UGT, FMO), inhibition of activity by specific inhibitors (CYP, FMO)
Identification of CYP isoforms
Enzyme evaluated
CYP
Enzyme sources
Human liver microsomes, CYP-expressing enzymes
Evaluation items
Identification using human CYP-expressing microsomes, identification using inhibitors, identification by correlation analysis

In vitro human CYP induction

We evaluate the effects of the test substance on drug metabolizing enzymes in vitro using human hepatocytes.

Evaluation item
Induction of CYP activities by measuring mRNA expression levels.

In vitro skin permeability

We evaluate skin permeability and transitivity of the test substance in vitro using human and experimental animal skin. In combination with in vivo (rat) dermal dosing studies, dermal absorption rates can also be estimated in humans in vivo (triple-pack). Test results required for pesticide registration (including reevaluation) are obtained in compliance with GLP standards for pesticides.

Metabolite profiling

In vivo metabolite profiling

We perform metabolite profiling in plasma, urine, feces, bile and organs obtained from animals treated with the test substance.

Animals used
Mice, rats, dogs, monkeys, rabbits, etc.
In vitro metabolite profiling

We perform in vitro metabolite profiling using hepatocytes or cell fractions from humans and various experimental animals to evaluate species and sex differences in the metabolism of the test substance.

Animals used
Humans, mice, rats, dogs, monkeys, rabbits, etc.
Enzyme source
Hepatocytes, microsomes (liver, kidney, small intestine, etc.), and S9 (liver, kidney, etc.)"

Other Services

Knowledge service

We provide technical guidance on ADME experiments (administration of RI labeled compounds, blood sampling, QWBA, and tissue, urine, feces, bile collection etc.).

Partnership with Nemoto Science Co., Ltd.

Mediford Corporation and Nemoto Science have signed a mutual master subcontract agreement for ADME Studies. This enables us to propose more various techniques and flexible timelines for studies.