PK/ADME Services

Our Indianapolis neighbors AIT Bioscience have partnered with us to provide complete PK/ADME services to accelerate you drug discovery and development. Utilizing the in-vivo proficiency of PCO and cutting edge LC/MS analytical expertise of AIT Bioscience the collaboration gives the researcher a rapid, cost-effective blend of talents to fully assess the properties of chemical entities including Cmax, half-life, tissue distribution, and renal clearance.

Services Offered:

• PK/Exposure – for assisting with dose selection and frequency, and drug
• Absorption
• Metabolism
• Excretion
• Metabolite Identification
• In Vivo Drug Screening (cassette dosing of multiple scaffolds)

Benefits of Partnership:

• Facilities are within walking distance – transfer of samples withing minutes of collection
• Rapid turn around – Dosing to Data within 15 days
• Cost effective
• Methods established for the collection and analysis of small sample volumes

Losartan Case Study

Goal: Evaluate the effect of a CYP2C9 inhibitor (phenylbutazone) on plasma levels of losartan and its active metabolite.

• Twelve Wistar rats were divided into 2 dosing groups.
• The first group received 10 mg/kg doses once daily for 15 days; PK samples were taken on the 15th day.
• The second group received a combination dose of 10 mg/kg losartan and 50 mg/kg phenylbutazone for 15 days once daily; PK samples were taken on the 15th day.
• The expected plasma concentrations were not expected to exceed 1000 ng/mL. Cmax for losartan is approximately 1.5 hours and 3-4 hours for the EXP3174 metabolite.
• Based on an elimination half-life of approximately 2 hours, samples were planned to cover the first 12 hours after dose.

AIT Method: To conserve sample, AIT developed a method in K2EDTA rat plasma that covered 1-1000 ng/mL using a 20 µL sample size. The method used deuterated internal standards for both analytes and liquid-liquid extraction. Extracts were analyzed on a UPLC-MS/MS system using gradient elution and electrospray ionization (Waters Acquity and Thermo Vantage systems).