In Vivo Pharmacokinetic Assays

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Services

• Multi-cycle cross BE/prescription screeningTissue distribution/blood-brain barrier permeability Kp,uu (in vivo fraction)Excretion studies/in vivo metabolite identificationIn vivo drug interactionsPK/PD in tumor-bearing rats125I/14C/3H labeled isotope drug PK/tissue distribution/material balanceLarge animal monkey/canine ultrasound-guided liver biopsyLarge animal monkey/canine muscle biopsyRapid screening or IND support

Species

• Mouseratguinea pigrabbitdogmini-pigcrab-eating macaque

Administration Routes

• Intravenoussubcutaneoustransdermalintramuscularintraperitonealoralsublingualnasalintravitrealintrathecal drug deliveryCassette administration

Sampling

• continuous microblood collection

Surgical Models

• Intravenous cannulationinfusion pumpbile duct cannulation

Feature Platforms

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  The Pharmacokinetics Research of Inhalation Drug

  Medicilon has significant experience in the research and development of inhaled drugs. Before testing, we will conduct a preliminary exploration of particle size, concentration, and aerosol generation.

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  The Pharmacokinetics Research of Ophthalmic Drug

  In terms of species selection, Medicilon has mice, rats, rabbits (Dutch bunted rabbit, New Zealand white rabbit), monkeys, dogs, miniature pigs and other animals to carry out ophthalmic drug substitution research.

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  The Pharmacokinetics Research of Nucleic Acid Drugs

  The Medicilon Liver Biopsy Guided By B-ultrasound In Cynomolgus Monkeys Platform can avoid the large blood vessels and gallbladder and has the advantages of less trauma, safe and simple puncture operation, accurate positioning, and better postoperative recovery.

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  Pharmacokinetic Study of Cell & Gene Therapy Drugs

  The pharmacokinetc research studies sample in vivo behaviors, such as distribution, proliferation and survival time. We also track transgenic product expressed and secreted outside of the immune cells to assess its local and/or systemic exposure characteristics.

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  The Pharmacokinetics Research of PROTACs Drug

  We can further characterise PROTAC molecules by using our integrated preclinical services including PK/PD studies, pharmacological analysis, pharmacokinetic studies, and safety evaluation.

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• The Pharmacokinetics Research of ADC Drug
  Due to molecular complexity, the PK characteristics of an ADC must be evaluated by multiple analytes. Therefore, the difficulty of analysis is increased. In in vivo assays for ADC, we have established a variety of quality testing methods for 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

Evaluation performance

• Our Preclinical Pharmacokinetics Department can complete approximately 1,000 single pharmacokinetic researches in vivo and 200 complete pharmacokinetic researches in accordance with the filing every year.The candidate categories we test include micromolecule drugs, bio-tech-based drugs and natural product drugs.The contents involved in evaluation include but are not limited to haemodynamics, tissue distribution, excretion  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.

Service Cases

Learn more about "In Vivo Pharmacokinetic Assays"

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  [Video]What happened when AUC suddenly  dropped in the repeated adminitration PKTK test

  

  [video]Medicilon's Bioanalysis and Pharmacokinetics Services

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 features of an ideal DMPK?

  (1) Complete absorption (preferably passive absorption), bioavailability > 50% and minimal variation;

  (2) AUC is proportional to dose, and there is a clear PK/PD correlation;

  (3) Quickly reaches the target organ and do not accumulate outside it;

  (4) PPB < 90%, unaffected by concentration and time;

  (5) Plasma clearance CL < 30% of Q_h, cleared through various routes;

  (6) Age, race, gender, disease state, etc. have little effect on CL; low quantity of metabolites and no production of reactive metabolites;

  (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) T_1/2>6hr in human body, reducing the dosing frequency and improving 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.

  
  

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