biostudies-literatureMangoni AATour de Cure Research, Support, and Prevention, Senior Research Grant1017https://www.ebi.ac.uk/biostudies/studies/S-EPMC8840040biostudies-literatureUnknown27(3)The pharmacokinetic profile of ZST316 and ZST152, arginine analogues with inhibitory activity towards human dimethylarginine dimethylaminohydrolase-1 (DDAH1), was investigated in mice using a newly developed HPLC-MS/MS method. The method proved to be reproducible, precise, and accurate for the measurement of the compounds in plasma and urine. Four-week-old female FVB mice received a single dose of ZST316 and ZST152 by intravenous bolus (30 mg/Kg) and oral gavage (60 mg/Kg). ZST316 Cmax was 67.4 µg/mL (intravenous) and 1.02 µg/mL (oral), with a half-life of 6 h and bioavailability of 4.7%. ZST152 Cmax was 24.9 µg/mL (intravenous) and 1.65 µg/mL (oral), with a half-life of 1.2 h and bioavailability of 33.3%. Urinary excretion of ZST152 and ZST316 was 12.5%-22.2% and 2.3%-7.5%, respectively. Molecules (Basel, Switzerland)Pharmacokinetic Characterization of the DDAH1 Inhibitors ZST316 and ZST152 in Mice Using a HPLC-MS/MS Method.PMC8840040RSP-246-18/19Mangoni AAZucchetti MTommasi SFichera SRusso MCeruti TFrapolli RfalsePharmacokinetic Characterization of the DDAH1 Inhibitors ZST316 and ZST152 in Mice Using a HPLC-MS/MS Method.The pharmacokinetic profile of ZST316 and ZST152, arginine analogues with inhibitory activity towards human dimethylarginine dimethylaminohydrolase-1 (DDAH1), was investigated in mice using a newly developed HPLC-MS/MS method. The method proved to be reproducible, precise, and accurate for the measurement of the compounds in plasma and urine. Four-week-old female FVB mice received a single dose of ZST316 and ZST152 by intravenous bolus (30 mg/Kg) and oral gavage (60 mg/Kg). ZST316 Cmax was 67.4 µg/mL (intravenous) and 1.02 µg/mL (oral), with a half-life of 6 h and bioavailability of 4.7%. ZST152 Cmax was 24.9 µg/mL (intravenous) and 1.65 µg/mL (oral), with a half-life of 1.2 h and bioavailability of 33.3%. Urinary excretion of ZST152 and ZST316 was 12.5%-22.2% and 2.3%-7.5%, respectively. 2022-01-01T00:00:00Z2022 Feb2025-04-25T23:01:30.112Z2025-04-06T09:13:41.239ZS-EPMC88400403516427710.3390/molecules27031017