1-Aminocyclopropanecarboxylic acid: mouse to man interspecies pharmacokinetic comparisons and allometric relationships.
1-Aminocyclopropanecarboxylic acid (ACPC) is a partial agonist at the strychnine-insensitive glycine recognition site on the N-methyl-D-aspartate (NMDA) receptor complex in the mammalian central nervous system with preclinical activity in animal models of neuroprotection and psychiatric illnesses. The pharmacokinetics of ACPC were studied in the rat, beagle dog, cynomolgus monkey, and human, and compared also with data from the literature for the mouse. Plasma elimination half-lives were 1.5, 2.5, 2.9, 20.3, and 5.9 h for the mouse, rat, monkey, dog, and human, respectively. Volume of distribution at steady state (0.74 L/kg) was constant across all species. Clearance values were consistent with glomerular filtration rates for all species, except in the dog, where clearance is consistent with 84% tubular reabsorption. Allometric relationships for clearance and half-life versus body weight confirmed the predictability of the pharmacokinetics of ACPC in the mouse, rat, monkey, and human. Continued clinical evaluation of ACPC as a neuroprotective agent and in a variety of psychiatric illnesses is warranted.
Cherkofsky
S C
SC
Symphony Pharmaceuticals, Inc., Malvern, PA 19355, USA.
D000596:Amino Acids / Q000097:blood / Q000493:pharmacokinetics*; D000598:Amino Acids, Cyclic; D000818:Animals; D004285:Dogs; D005260:Female; D006207:Half-Life; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution
D000596:Amino Acids; D000598:Amino Acids, Cyclic; C023863:1-aminocyclopropane-1-carboxylic acid