Absorption, Distribution, Metabolism, Excretion (ADME), Drug-drug interaction potential and Prediction of Human Pharmacokinetics of SUVN-G3031, a Novel Histamine 3 Receptor (H3R) inverse agonist in Clinical development for the treatment of Narcolepsy.

Absorption, Distribution, Metabolism, Excretion (ADME), Drug-drug interaction potential and Prediction of Human Pharmacokinetics of SUVN-G3031, a Novel Histamine 3 Receptor (H3R) inverse agonist in Clinical development for the treatment of Narcolepsy. Eur J Pharm Sci. 2020 Jun 10;:105425 Authors: Nirogi R, Bhyrapuneni G, Muddana NR, Manoharan A, Shinde AK, Mohammed AR, Padala NP, Ajjala DR, Subramanian R, Palacharla VRC Abstract SUVN-G3031 is a potent and selective inverse agonist of Histmine-3 (H3) receptor that is being investigated for the treatment of narcolepsy. SUVN-G3031 has high passive permeability, not a substrate for P-glycoprotein, has high plasma unbound fractions and was equally distributed between blood and plasma. Major routes of metabolism in vitro were cyclization (Metabolite A) in microsomes and dealkylation (Metabolite D) in hepatocytes. Intrinsic clearance in liver microsomes and hepatocytes was low as monitored by metabolite formation approach. CYP3A4 and MAO-A were the major enzymes involved in the formation of metabolite A and metabolite D respectively. The human hepatic clearance estimated by well-stirred model from hepatocytes was low (2.7 L.h-1) illustrating the importance of metabolite formation kinetics for prediction of human clearance for SUVN-G3031. Renal clearance in humans (9.7 L.h-1) was predicted from dog renal clearance and accounts for ∼78% of the total clearance. SUVN-G3031 was neither an inhi...
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research