Pharmacokinetic-Pharmacodynamic Modeling of the Electroencephalogram Effect of Imipenem in Healthy Rats

• DOI: 10.1128/aac.45.6.1682-1687.2001
• Publication Date: 2002-07-27T10:06:42Z
• Authors: Antoine Dupuis; William Couet; Joël Paquereau; Stanley Debarre; Agnès Portron; Candice Jamois; Serge Bouquet
• Keywords: Pharmacodynamics

A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was developed to investigate the epileptogenic activity of imipenem in rats. Initially, animals received an intravenous infusion at a rate 2.65 mg min(-1) for 30 min. Blood samples were collected drug assay, and electroencephalogram (EEG) recorded during postinfusion. dramatic delay observed between concentrations serum EEG effect; this effect accompanied by tremors partial seizures. Indirect-effect models failed describe these data, which successfully fitted using compartment model. The relationship concentration site best described spline function. elimination constant from severalfold lower than that central compartment. robustness model then confirmed after administering dose over 60 90 In conclusion, successful PK-PD rats constitutes major improvement better prediction risk associated with antibiotic.