Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, a Potential Oral Drug Candidate for COVID-19 Treatment

• DOI: 10.3389/fphar.2022.918083
• Publication Date: 2022-08-16T07:27:43Z
• Authors: Amy Q. Wang; Natalie R. Hagen; Elias C. Padilha; Mengbi Yang; Pranav Shah; Catherine Z. Chen; Wenwei Huang; Pramod Terse; Philip Sanderson; Wei Zheng; Xin Xu
• Keywords: Drug candidate; 2019-20 coronavirus outbreak

Preclinical pharmacokinetics (PK) and In Vitro ADME properties of GS-441524, a potential oral agent for the treatment Covid-19, were studied. GS-441524 was stable in vitro liver microsomes, cytosols, hepatocytes mice, rats, monkeys, dogs, humans. The plasma free fractions 62-78% across all studied species. transporter study results showed that substrate MDR1, BCRP, CNT3, ENT1, ENT2; but not CNT1, CNT2, ENT4. had low to moderate clearance (CLp), ranging from 4.1 mL/min/kg dogs 26 mice; steady state volume distribution (Vdss) ranged 0.9 L/kg 2.4 mice after IV administration. Urinary excretion appeared be major elimination process GS-441524. Following administration, bioavailability 8.3% 33% 39% 85% dogs. PK support its further development as an drug candidate.