Implementation of automated blood sampling in a canine cardiovascular safety pharmacology study to support PK/PD assessment
Abstract
INTRODUCTION: Pharmacokinetic (PK) and pharmacodynamic (PD) modeling can elucidate the temporal interplay between drug concentration and physiological effects. Its use in safety pharmacology studies has been hindered, since collecting an adequate number of blood samples from conscious animals poses challenges. This study introduces an automatic blood sampling system into a cardiovascular safety pharmacology study to enable the collection of frequent blood samples from conscious animals to allow for a PK/PD assessment.
METHOD: For this investigation, we employed a telemetry-based approach to obtain cardiovascular data from 4 Beagle dogs. To assess the PK profile of the test compound, an automated blood sampling device was used to facilitate the collection of up to 20 blood samples at predefined time points over the 7-h study period. The cross-over study was conducted using conscious, freely-moving animals, with Moxifloxacin administered as the test compound.
RESULTS: Moxifloxacin administered orally in doses of 10 mg/kg, 30 mg/kg and 100 mg/kg reached Cmax of 6340 ± 1087, 15,840 ± 5471 and 29,033 ± 6540 nM, respectively, resulting in a QTc prolongation of 7 ms for 10 mg/kg, 17 ms for 30 mg/kg and 35 ms for 100 mg/kg. Based on the PK/PD analysis, a 5 ms QTc prolongation occurs with a Moxifloxacin concentration of 6.2 μM and a 10 ms QTc prolongation occurs with 12 μM. The feasibility of integrating automated blood samples in a cardiovascular safety pharmacology study using…
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.