Overview

BioDuro provides insightful Drug Metabolism and Pharmacokinetics services through its unique position as a drug discovery and preclinical 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 studies in an AAALAC accredited and GLP-like environment and a full in vitro ADME assay platform

BioDuro Advantage

• Assay platform spanning from discovery to preclinical development
• The state-of-art and GLP-like bioanalytical laboratory
• AAALAC accredited animal facilities
• Over 14-year history of execution, flexibility and timeliness
• Rapid turnaround time
• Cost-effective

Physicochemical properties

• Kinetic and thermodynamic solubility
• LogD
• pKa
• Chemistry stability

Metabolic stability

• Hepatocyte stability
• Liver microsomal stability
• recombinant CYP450 stability
• Liver S9 fraction stability
• Intestine microsomal stability
• Plasma stability
• Blood stability

Permeability measurement

• PAMPA
• Caco-2
• MDR1-MDCK

Distribution

• Plasma protein binding
• Microsomal protein binding
• Tissue protein binding
• Red blood cell partition (RBC)

Transporters

• P-gp/Caco-2
• BCRP/Caco-2
• MDR1/MDCK
• BSEP/vesicles
• MRP2/vesicles
• OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2K/HEK293

Drug-drug interactions

• CYP450 inhibition (inhibition% or IC50)
• CYP450 time dependent inhibition (inhibition% or IC50 shift)
• CYP450 induction using cryo-preserved human hepatocytes

Metabolite identification and profiling

• Metabolite identification in liver microsomes and other in vitro metabolic reaction systems
• Metabolite identification in plasma and other fluids or tissues from PK or TK studies
• Reactive metabolite GSH trapping

Reaction phenotyping

• CYP450 reaction phenotyping (rhCYP and chemical inhibition)
• UGT reaction phenotyping

Turnaround Time

• 5 working days except metabolite identification and uptake transporter (10 working days), and CYP450 induction (15 working days)

Rodents

• 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), OA (oropharyngeal aspiration), Intrarectal (IR), intranasal (IN), single or multiple doses
• 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

Large Animal PK/TK

• Dogs:
  • In-house dog colony: 48 Beagle dogs
  • Administration Routes: PO and IV (bolus, infusion), SC, IM
  • Crossover or Non-crossover; fast/fed (food effect); PK/PD evaluation
• Monkeys:
  • Off-site NHP colony: 32 Cynomologus monkeys (Rhesus monkeys also available)
  • Partner: Dosing and sampling
  • BioDuro: Formulation preparation, 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) (samples analyzed by partners)
  • 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)
• Drug-drug inhibitory interaction
• PD biomarkers

Capacity

• 60 IV/PO PK/week

Pre-formulation screening

• ~2,000 compounds/year

Other species available with Partners

• Ferrets
• Mini-pigs
• Rabbits

IND-enabling ADME/PK studies (US and China FDA Filing)

Equipment

• LC-MS/MS
  • API-6500+
  • API-5500
  • API-4000 QTRAP
  • API 4500 QTRAP
  • API 4000
  • Q-Exactive Plus (HRMS)
• UPLC/UHPLC/HPLC
  • Waters H-Class
  • Shimadzu LC-30AD and LC-20AD
  • UltiMate 3000