Pharmacokinetics of esomeprazole following intravenous and oral administration in healthy dogs

Abstract

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.

Preclinical Evaluation of Esomeprazole Safety and Toxicokinetics

“…В ходе проведенного исследования кроме сравнительной оценки общетоксических свойств и местнораздражающего действия было изучено влияние воспроизведенного препарата эзомепразол и препарата сравнения Нексиум® на иммунокомпетентные органы с целью выявления возможного иммунотоксического действия 18 . Полученные результаты позволили заключить, что при введении в дозах, соответствующих примерно 4,8 и 14,3 ВТД в течение 28 сут, препараты не оказали иммунотоксического действия.…”

“…Наиболее устойчивые различия выявлены для параметра Т max -в большинстве случаев различия этого параметра для тестируемого препарата и препарата сравнения статистически В целом полученные данные сопоставимы с результатами, известными для человека, согласно которым эзомепразол достаточно быстро всасывается из желудочно-кишечного тракта -T max составляет примерно 0,5-2,5 ч после приема, при ежедневном приеме 1 раз/сут эзомепразол полностью выводится из плазмы крови во время интервала между приемами и не кумулирует [10,16,17,[20][21][22][23]. Схожие данные получены для некоторых видов лабораторных животных -собак и крыс [18,24,25].…”

Novel Esomeprazole Magnesium-Loaded Dual-Release Mini-Tablet Polycap: Formulation, Optimization, Characterization, and In Vivo Evaluation in Beagle Dogs

“…Pentagastrin lowers the dog stomach pH within 30 min after intramuscular injection, simulating the pH of the human stomach and reducing the variability in absorption in dogs [ 31 ]. In addition, one study suggested that when healthy dogs were administered EMP without pentagastrin, two different populations were observed: those that demonstrated lag absorption and those that did not [ 32 ]. After administration, approximately 1.0 mL of blood was collected from the dogs’ head vein at predetermined intervals.…”