Novel protocol for multiple-dose oral administration of the L-type Ca²⁺ channel blocker isradipine in mice: A dose-finding pharmacokinetic study.

ABSTRACT: Studies in genetically modified animals and human genetics have recently provided new insight into the role of voltage-gated L-type Ca²⁺ channels in human disease. Therefore, the inhibition of L-type Ca²⁺ channels in vivo in wildtype and mutant mice by potent dihydropyridine (DHP) Ca²⁺ channel blockers serves as an important pharmacological tool. These drugs have a short plasma half-life in humans and especially in rodents and show high first-pass metabolism upon oral application. In the vast majority of in vivo studies, they have therefore been delivered through parenteral routes, mostly subcutaneously or intraperitoneally. High peak plasma concentrations of DHPs cause side effects, evident as DHP-induced aversive behaviors confounding the interpretation o

SUBMITTER: Theiner T 

PROVIDER: S-EPMC10989688 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature