In vivo (studies using labeled compounds)

We calculate the pharmacokinetic parameters based on total plasma radioactivity concentration, unchanged drug concentration and its metabolite concentrations in samples obtained through multiple blood collections over time from an identical animal (feasible in various animal species). Then, the absorption rate, linearity, bioavailability and gender difference can be discussed in combination with the excretion study results. We will examine the absorption site as required.

We calculate peak plasma concentration (Cmax), time to peak plasma concentration (Tmax) and area under the concentration-versus-time curve (AUC). Then we evaluate the linearity of absorption, absorption rate, first-pass effect, extent of absorption and bioavailability through comparison of various parameters using intravenous administration or an administration route in which the absorption process is negligible.
Pharmacokinetic parameters can be analyzed using WinNonlin.

We examine absorption sites using the gastrointestinal loop method.

We examine the distribution of a drug and its metabolites into various tissues, the changes over time, the remaining drug level and plasma protein binding rate.

We examine the ratios of various tissue concentrations to the plasma concentration at multiple time points including Tmax, 24 hours after administration and completion of the excretion, and the change over time. In tissues with a high level of remaining drug, the chemical status of the drug will be examined.

We examine the whole image of drug distribution, its accumulation in the tissues, and the localization of radioactivity in the tissue. Localization of the radioactivity in microtissues, etc. can be clarified.

We examine the radioactivity distribution in the target tissues at the light microscopic level (liver, kidney, skin, artery, tumor, small intestine, pancreas, adrenal gland, thymus, stomach, bone, brain, etc.)

We examine the plasma protein binding rate with plasma and purified protein from various animal species using the equilibrium dialysis method, ultrafiltration method or ultracentrifugal method.

We examine drug partitioning into blood cells using blood from various animal species (in vitro/in vivo).

We examine changes over time in drug partitioning into lymph vessels by cannulation into the lymph vessels.

We examine the metabolism profile using plasma, major tissues and excrement to see to what extent the drug is metabolized in an animal.

We establish the analysis methods using HPLC-RAD and LC/MS/MS.

We confirm the reproducibility of the analysis based on your analysis conditions.

We examine profile of unchanged drug and its metabolites in plasma, urine, bile and tissues, and their proportions.

We estimate the structure of metabolites using LC/MS/MS.

We determine excretion rates into urine, feces, expiration and bile, and examine excretion route, absorption rate and excretion speed of the unchanged drug and its metabolites. If the main excretion route involves bile, enterohepatic circulation will be examined as well.

In principle, determination covers a time point when at least 95% of the dose given is excreted or 7 days is passed after administration, and at the same time the percentage of in vivo remaining drug is determined.

We examine the excretion route and absorption rate of drug.
Examination using the free-moving method is possible.

We search for human-specific metabolites through the pharmacokinetic study of a candidate compound using a chimeric mouse with human hepatocyte.
YA Kimera.pdf [164KB]

We conduct/examine the transfer of a candidate compound into the fetus during the period of organogenesis or the perinatal period in pregnant rats following administration by various routes (oral, intravenous, subcutaneous, transdermal, etc.), based on tissue distribution (tissue concentration and wholebody autoradiography). We have studied excretion in milk of a candidate compound in lactating rats following administration by various routes (oral, intravenous, subcutaneous, transdermal, etc.).

We examine the accumulation and retention of a candidate compound through the determination of plasma and tissue concentrations, examination of excretion into urine, feces and expiration and wholebody autoradiography in animals (rat, dog, monkey and rabbit) following administration by various route (oral, intravenous, subcutaneous, transdermal, instillation, etc.).

We can conduct a pharmacokinetic study with conventional administration/microdosing of a labeled compound in overseas human clinical centers.

AMS has allowed the measurement of radioactive compound in plasma, feces, tissue, etc. at low level, which conventional liquid scintillation counters cannot achieve. It is an especially useful analysis method in human pharmacokinetic studies on microdosing.
^*Accelerator Mass Spectrometry