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ADME studies and preliminary safety pharmacology of LDT5, a lead compound for the treatment of benign prostatic hyperplasia BJMBR
Noël,F.; Nascimento-Viana,J.B.; Romeiro,L.A.S.; Silva,R.O.; Lemes,L.F.N.; Oliveira,A.S.; Giorno,T.B.S.; Fernandes,P.D.; Silva,C.L.M..
This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity). LDT5 is stable in...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Benign prostatic hyperplasia; ADME; Safety; Permeability; CYP; Preclinical development.
Ano: 2016 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016001200603
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