Investigation into the pharmacokinetic profile of esomeprazole was conducted using eight healthy dogs after intravenous (IV) and oral (po) administration in a two-part randomized crossover study. The dogs were fasted for a minimum of 12 hours and then received esomeprazole either intravenously (dose range 0.93-1.48 mg/kg) or orally using an enteric-coated formulation (dose range 0.95-1.50 mg/kg). After a 1-week washout period, the dogs received an alternative treatment. Serial blood samples were collected at predetermined time points, and plasma esomeprazole concentrations were determined by using ultra-high-performance liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Then, the area under the plasma concentration/time curve (AUC) and maximal plasma concentration (Cmax) values were normalized to a 1.0 mg/kg dose of esomeprazole, that is, AUC/dose. Median (range) dose-normalized peak plasma concentration (Cmax) values for the IV and po formulations were 4.06 µg/mL (2.47-4.57 µg/mL) and 1.04 µg/mL (0.31-1.91 µg/mL), respectively. The median (range) time-to-peak concentration (Tmax) for the po formulation was 105 minutes (45-360 minutes). Median (range) plasma terminal half-life (t½) was 45.56 minutes (39.43-64.20 minutes) for the IV formulation and 63.97 minutes (44.02-109.94 minutes) for the enteric-coated po formulation. The median (range) po bioavailability was 63.33% (32.26%-79.77%). Clinically, both po and IV formulations were well tolerated with minimal side effects observed.
Keywords: and oesophagitis; gastric ulcers; proton pump inhibitors.