In Vivo Pharmacokinetic Assays

Medicilon has rich experience in pharmacokinetics research. We offer a broad spectrum of high quality of services involving all micromolecule and macromolecule (protein and antibody), with service contents including in vitro ADME, in vivo pharmacokinetics and bioanalysis. The test subjects involved include non-human primates, dogs, rats/mice, rabbits and guinea pigs. Among them, the non-human primate experimental platform and the isotope platform for protein/antibody have been recognized as important laboratory platforms by Shanghai Municipal People's Government.

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Services

Haemodynamics ResearchTissue Distribution ResearchExcretion ResearchMaterial BalanceBlood Brain BarrierADC pharmacokinetic evaluation, etc.

Due to complex compositions, the PK characteristics of ADC must be evaluated by multiple analytes. Therefore, the difficulty of analysis is increased. In the in vivo assay of ADC, we have provided a variety of quality testing methos for various ADC component analytes. By analyzing plasma/serum samples collected from animals, we provide our clients with reliable and quality PK data.

Determinand	Description	Typical analysis method
Conjugated Antibody	Antibody conjugated to at least one drug	LBA
Total Antibody	Fully conjugated, partially conjugated and unconjugated antibodies	LBA
Small Molecules	Free or diluted drug micromolecules and their metabolites	LC-MS/MS
ADA	Antibodies that can specifically bind ADC molecules and their partial structures	LBA

In the meantime, Medicilon has introduced an animal in vivo PET/CT/MR molecular imaging system. Through the system, the delicate and complex physiological and metabolic processes in organisms can be observed. The PET research with radio-tracer label can ensure quantitative evaluation of the pharmacokinetics and metabolism of drugs. Combined with efficacy data including ethology performance, the pharmacokinetics PET researcher can establish the dose-efficacy relationship and determine the dose while tracking the regional distribution of drugs in target tissues.

Evaluation performance

Our Preclinical Pharmacokinetics Department can complete nearly 1,000 single pharmacokinetic researches in vivo and nearly 200 complete pharmacokinetic researches in accordance with the filing every year.The research categories involve micromolecule drugs, bio-tech-based drugs and natural product drugs.The contents involved in evaluation include but are not limited to haemodynamics, tissue distribution, rxcretion and material balance.Medicilon have a research license for radioisotopes (125I, 14 C, 3H). The license is for material balance and tissue distribution researches.

Software

WinNolin and WastonLim are used for calculation and processing of pharmacokinetic research data and management of analytical laboratory.

FAQ

What is Caco-2 Cell Model?

The Caco-2 cell line is a human colon adenocarcinoma epithelial cell that can differentiate itself into a monolayer similar to a mature human small intestinal epithelial cell.
What are the Ideal DMPK Properties?

(1) Complete absorption (passive absorption is better), bioavailability > 50% and small variation;
(2) AUC is proportional to dose, and PK/PD correlation is clear;
(3) Quickly reach the target organ and do not accumulate outside the target organ;
(4) PPB<90%, not affected by concentration and time;
(5) Plasma clearance CL<30%Qn, cleared through various routes;
(6) Age, race, gender, disease state, etc. have little effect on CL;
(7) metabolite quantity is low and no reactive metabolites are produced;
(8) Does not inhibit or induce major drug metabolizing enzymes and transporters, and is not affected by food;
(9) T1/2>6hr in human body, which can reduce the dosing frequency and improve the compliance.
What is the Explanation for the Clearance (CL) > Hepatic Blood Flow (Qh) in the In Vivo PK Test in Animals?

(1) The liver is the main organ of drug metabolism, but not the only way of drug elimination. There is also renal elimination, etc.
(2) The drug is unstable in the blood, and the clearance of the drug does not have a hepatic effect.
(3) In some cases, when the drug concentration in red blood cells is much higher than that in plasma, the calculation of proper clearance cannot be approximated by the drug concentration in plasma.
(4) In individual cases, metabolism or uptake by the lungs occupies a significant role.
What Should Explain Bioavailability F > 100% in Animals' In Vivo PK Test?

(1) Dose deviation due to administration error.
(2) Nonlinear pharmacokinetics (Nonlinear PK).
(3) High bioavailability and individual variability in the DMPK properties of the drug, with IV and PO, given to different groups of animals.
(4) Overestimation of PO AUC or underestimation of IV AUC due to unreasonable sampling points.
(5) IV samples were left for extended periods, and compounds were unstable in plasma.
(6) When administered as a racemate, the faster-clearing enantiomer is converted to the slower-clearing enantiomer in the GI tract.

Relevant laboratories

Relevant articles

In Vitro Pharmacokinetic Assays In Vivo Pharmacokinetic Assays