Overview

BioDuro provides insightful Drug Metabolism and Pharmacokinetic services through its unique position as a drug discovery and development organization. With strong credentials and experience in chemistry, biology, pharmacology, and formulation development, the DMPK team performs studies with a wide variety of animal models in an AAALAC accredited and GLP-like environment.

BioDuro Advantage

• Integration with drug discovery and drug development teams
• 5-10 day project turnaround time
• Custom studies for ADME
• AAALAC accredited animal facilities
• GLP-like laboratory environment
• Dedication to animal welfare

Services

• In Vitro ADME
  • Physicochemical properties
    • Kinetic and thermodynamic stability
    • LogP, LogD
    • pKa
  • Metabolic stability
    • Hepatocyte stability assay
    • Microsomal stability assay
    • rCYPs
    • S9
    • Plasma stability assay
  • Permeability measurement
    • Caco-2
    • PAMPA
    • MDR1-MDCK *new offering*
  • Distribution
    • Plasma protein binding
    • Microsomal and tissue protein binding
    • Red blood cell partition (RBC)
  • Transporter assay
    • OATP1B1/HEK293
    • BCRP/MDCK
    • MDR1/MDCKII
  • Drug-drug interaction
    • Cytochrome P450 time dependent inhibition assay (single-point or IC50 shift)
    • Cytochrome P450 inhibition assay (DDI)
• In Vivo Rodent PK/TK
  • Species:
    • Mice (CD-1, C57BL/6, etc), Rats (Sprague Dawley, Wistar, Wistar-Han, etc), Hamsters, Guinea pigs
  • Administration Routes:
    • Oral (PO), Intravenous (IV bolus, infusion, cassette-dosing), Intraarterial (IA), intramuscular (IM), Intraperitoneal (IP), Intratracheal (IT), Subcutaneous (SC), Transdermal (TD)
  • Surgical Techniques:
    • Bile-duct cannulation (BDC), Jugular cannulation (JVC), Portal vein cannulation (PVC), Carotid artery cannulation (CAC), JVC/CAC, JVC/PVC
  • Biological Matrices:
    • Blood plasma/serum, bile/urine/feces, cerebrospinal fluid (CSF), bone marrow, tissue (liver, brain, kidney, etc) or tumor specimens
  • Mouse PK: Serial bleeding
  • Cassette-dosing
  • Excretion pathways
  • Turnaround Time:
    • 5-10 working days
• Dog and Monkey PK
  • Dog PK:
    • In-house dog colony: 48 Beagle dogs
    • Administration Routes: PO and IV (bolus, infusion), SC
    • Crossover or Non-crossover; fast/fed (food effect); PK/PD evaluation
  • Monkey PK:
    • Off-site NHP colony: 32 male Cynomologus monkeys
    • Partner: Dosing and Sampling
    • BioDuro: Formulation prep, monitoring for dosing and sampling, bioanalytical method development and sample analysis, report writing
    • Excretion pathways
  • Turnaround time:
    • 10 working days for non-naive dogs & monkeys
• Exploratory Toxicity (MTD, DRF) in Rodents (In-house) and in Dogs/Monkeys (With Partners)
  • Maximum toleration dose
  • Dose ranging finding/toxicokinetics (7, 14 and 28 days)
    • Clinical observation
    • Clinical pathology (serum chemistry, hematology and coagulation)
    • Histopathology (samples analyzed by partners)
  • Turnaround Time
    • 10 working days for TK and clinical pathology
    • 5-6 weeks for histopathology report
• Deliverables
  • Bioavailability
  • PK parameters
  • Tissue distribution
  • Maximum toleration dose
  • Dose proportionality
  • Excretion pathways: biliary vs urinary
  • Vehicle selection
  • Blood Brain Barrier (BBB)
  • PD biomarkers
• Capacity
  • 60 IV/PO PK/week
• Pre-formulation screening
  • ~2,000 compounds/year
• Other species available with Partners
  • Ferrets
  • Mini-pigs
  • Rabbits

Capabilities

• PO, IV, SC, IP, IN; IV/PO cassette dosing
• Multiple dosage routes
• Multiple cannulation models
• Liver microsome/hepatocyte stability
• CYP phenotyping
• Metabolite ID
• Caco-2
• PAMPA
• CYP inhibition assay
• Time dependent inhibition
• GSH trapping assay

Equipment

• LC-MS/MS
  • API-6500+
  • API-5500
  • API-4000 QTRAP
  • API 4500 QTRAP
  • API 4000
• UPLC/HPLC
  • Shimadzu LC-30AD
  • Waters H-Class
  • Shimadzu LC-20AD