Fast mouse PK (Fast PK): a rapid screening method to increase pharmacokinetic throughput in pre-clinical drug discovery.
We describe a rapid screening methodology for performing pharmacokinetic (PK) studies in mice called Fast PK. In this Fast PK method, two mice were used per compound and four blood samples were collected from each mouse. The sampling times were staggered (sparse sampling) between the two mice, thus yielding complete PK profile in singlicate across eight time points. The plasma PK parameters from Fast PK were comparable to that obtained from conventional PK methods. This method has been used to rapidly screen compounds in the early stages of drug discovery and about 600 compounds have been profiled in the last 3 years, which has resulted in reduction in the usage of mice by 800 per year in compliance with the 3R principles of animal ethics. In addition, this Fast PK method can also help in evaluating the PK parameters from the same set of animals used in safety/toxicology/efficacy studies without the need for satellite groups.
DMPK, Infection Innovative Medicines, AstraZeneca India Pvt. Ltd., Kirloskar Business Park, Hebbal, Bangalore 560 024, India.
Jitendar
J
Reddy
Sreedhar
S
Madishetti
Prakash R
PR
Vachaspati
D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
D004364:Pharmaceutical Preparations; D012293:Rifampin