Pharmacokinetic Study

Based on expertise that has been accumulated since the start of contract pharmacokinetic studies in 1971, we conduct various such studies.
Please contact us about conducting a kinetic study using pathologic animals.

• Article 43 "Quality Assurance Standard for application materials," Enforcement Regulation of the Japanese Pharmaceutical Affairs Law (MHW Ordinance No.1)
• OECD Principles on Good Laboratory Practice (revised 1997, Issued Jan 1998)
  ENV/MC/CHEM (98) 17

We conduct absorption, distribution, metabolism and excretion studies using various animal species.

• Isotope: ¹⁴C, ³H, ¹²⁵I, etc.

For the other isotopes, please ask us.

• Animal species: rat, mouse, dog, monkey and miniature pig
• Administration route: oral, intravenous, continuous intravenous, transdermal, subcutaneous, intramuscular, intratracheal, instillation, intrarectal and intraduodenal administrations, etc.

For the other administration routes, please ask us.
(e.g.: nasal, intra-aqueous chamber, intra-hepatic artery, intra-hepatic vein, intra-articulatio genus, etc.)

We conduct enzyme induction studies (rat) and drug concentration determination.

1) Drug concentration determination

2) Enzyme induction study

1) Estimation/Inhibition of CYP species

We estimate CYP species involved in the metabolism of a candidate compound using human P450 expression systems or human liver microsome. We examine the inhibition action of individual CYP species on specific substance metabolisms and evaluate inhibition constants (IC₅₀ or Ki) and time-dependent inhibition. Examinations will be conducted on FMO, MAO and UGT.

2) Transporter study

We investigate if a candidate compound can be used as a substance of individual transporter, using MDR1/P-gp expressing cells, OATP1B3-MRP2 co-expressing cells, transporter-expressing oocyte system or frozen human liver cells. We also examine the inhibiting action of a candidate compound on the transport of a probe reagent, and the inhibiting action of typical transporter inhibitors on the transport of a candidate compound to calculate inhibition constants (IC₅₀ or Ki). Evaluation of various ABC transporters and SLC transporters are possible.

3) Comparative metabolism study among various animal species

We examine and compare metabolite production/decrease in unchanged compound level among animal species (derived from mouse, rat, dog, monkey, human) using liver microsome, liver S9, cytosol and hepatocyte. Examination using cell fractions from non-liver tissues (kidney, small intestine and lung, etc.) is possible.

4) Enzyme induction study

We evaluate induction activity for the drug metabolizing enzyme of a candidate compound by measurements of enzymatic activity or mRNA level using frozen or non-frozen human culture hepatocytes.

5) Protein binding

We determine plasma the protein binding rate of a candidate compound in various animals and human by a number of study methods such as the equilibrium dialysis method, ultrafiltration method and ultracentrifugal method. The candidate’s affinity to HSA, α1-AGP and IgG, their binding sites and the number of such site can also be determined.