Early Pharmacokinetics

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  Radiolabel ADME
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Services we offer

• In Vitro ADMET
  AbsorptionCaco-2 permeabilityTransmembrane transport tests(Caco-2, P-gp, BCRP, OATs/OCTs/OATPs, etc.)DistributionProtein binding: plasma, tissue, and microsomesWhole blood/plasma distribution testsMetabolismMetabolic stability:(Liver microsome stability tests, S9 stability tests, Hepatocyte metabolic stability tests, Plasma stability tests)Matric stability: plasma, tissue, and bufferIn vitro metabolite profiling and identification(Metabolite speculation, Metabolite confirmation; Estimation of metabolic pathways, Confirmation of metabolic pathways)Drug-drug interaction(DDI)Cytochrome P450 (CYP) inhibition (IC₅₀ and TDI)P450 enzyme inductionEnzyme phenotyping: phase I and phase II enzymes (recombinant enzyme and chemical inhibition)Physicochemical properties （Lipophilicity, solubility tests）In vitro toxicity（hERG test, Mini-Ames）Rapid screening
• In Vivo PK
  Mouse/rat/guinea pig/rabbit/dog/mini-pig/crab-eating macaqueIntravenous / subcutaneous / transdermal / intramuscular /intraperitoneal / oral / sublingual / nasal / intravitreal / intrathecal drug deliveryIntravenous cannulation / infusion pump / bile duct cannulationCassette administration/continuous microblood collectionMulti-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

Service Platform

• The micromolecule analysis instrument platform represented by Sciex/Waters/Shimadzu ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and Thermo Q Exactive HF-X quadrupole/ultra-high-field fourier transform ion trap high-resolution mass spectrometry  The macromolecule analysis instrument platform represented by the MSD high-throughput multi-protein detector, Luminex liquid-phase chip protein analysis system, the Gyrolab nano-upgraded microfluidic immunoassay workstation and the Applied Biosystems real-time fluorescent quantitative PCR system  The sample pretreatment platform represented by the Covaris AFA adaptive focused acoustics high-performance sample processing system, the KingFisher Flex automatic magnetic bead extraction and purification system, the Lysera high-efficiency sample crusher and the TurboVap high-speed sample concentrator  The sample management platform composed of Thermo/Panasonic ultra-low temperature refrigerators, the SensaTronics temperature monitoring system and the Watson LIMS laboratory information management software

Cases

FAQs

• Why is Early DMPK Important?

  In 1991, up to 40% of failures in the clinical phase of new drug development were associated with drug DMPK properties; in 2000, the likelihood of late failure was dramatically reduced to less than 10% as major pharmaceutical companies shifted to early DMPK studies.

  (1) Early pharmacokinetic testing allows for a low-cost, short-term risk-benefit assessment of new drug development projects.

  (2) Guiding the processes from optimization of lead compounds to determination of preclinical drug candidates.

• What are the Six Major Types of Early DMPK Studies?

   (1) Protein binding: plasma, brain tissue, microsomal protein, FBS; Erythrocyte /plasma partition ratio

   (2) Optimization permeability and transshipment: Caco - 2. MDCK - MDR1 / BCRP, OATs/OCTs/OATPs

   (3) In vitro metabolic DDI: P450 inhibited TDI, P450 induced /PXR, metabolic enzyme phenotype.

   (4) Metabolic stability: microsomes, S9, hepatocytes, plasma, whole blood

   (5) Metabolite Screening and Identification: in vitro, in vivo, and GSH Trapping

   (6) In vivo PK: rat, mouse, dog, monkey, pig, rabbit box/single administration

  --- IV/IJVC/SC/TD/IM/IP/PO/SL/IN/IVT

  --- Continuous cross/single point blood sampling

  --- BBB(homogenate /CSF), Tissue distribution excretion (BDC), in vivo DDI (ABT)

  
  

• Can Medicilon Complete Preclinical DMPK Services?

  (1) 19⁺ years of accumulated experience.

  (2) Completing preclinical DMPK filing studies for about 20 new drugs per year.

  (3) In vivo PK screening of >2000 compounds per year.

  (4) One-stop service for PK/PD.

  (5) Antibody/ADC preclinical DMPK services.

  (6)Technical service solution for isotope drug metabolism research.

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