Quantitation of a Novel Engineered Anti-infective Host Defense Peptide, ARV-1502: Pharmacokinetic Study of Different Doses in Rats and Dogs

Quantitation of a Novel Engineered Anti-infective Host Defense Peptide, ARV-1502: Pharmacokinetic Study of Different Doses in Rats and Dogs

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The designer proline-rich antimicrobial peptide (PrAMP) Chex1-Arg20 amide (ARV-1502) is active against Gram-negative and Gram-positive pathogens in different murine infection models when administered parenterally and possesses a wide therapeutic index.Here we studied the pharmacokinetics of ARV-1502 for the first time when administered intramuscularly or intravenously (IV) in Sprague Dawley rats and Beagle dogs.First, a chicago cubs earrings specific and robust quantitation method relying on parallel reaction monitoring (PRM) using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer coupled on-line to reversed-phase uHPLC was established and validated.

The limit of detection was 2 ng/mL and the limit of quantitation was 4 ng/mL when spiked to pooled rat and dog plasma.When ARV-1502 was administered IV at doses of 75 and 250 μg/kg in dogs and read more rats, the plasma concentrations were 0.7 and 3.

4 μg/mL 2 min post-administration, respectively.ARV-1502 plasma concentrations declined exponentially reaching levels between 2 and 4 ng/mL after 2 h.Intramuscular administration of 0.

75 mg/kg in dogs and 2.5 mg/kg in rats resulted in a different pharmacokinetics profile.The plasma concentrations peaked at 15 min post-injection at 1 μg/mL (dogs) and 12 μg/mL (rats) and decreased exponentially within 3 h to 4 and 16 ng/mL, respectively.

The initial plasma concentrations of ARV-1502 and the decay timing afterwards indicated that the peptide circulated in the blood stream for several hours, at some point above the minimal inhibitory concentration against multidrug-resistant Enterobacteriaceae, with blood concentrations sufficient to suppress bacterial growth and to modulate the immune system.