Pharmacokinetic analysis of beta-aminopropionitrile in rabbits.
beta-Aminopropionitrile (beta APN), inhibits the activity of lysyl oxidase, an important enzyme for the post-translational formation of inter- and intramolecular covalent cross-linking between the connective tissue proteins, collagen and elastin. We became interested in the possible use of this compound as a therapeutic agent in the so-called human collagen diseases. beta APN's action mechanism is known, but its pharmacokinetics in rabbits have not yet been determined. The present study defined the kinetic parameters of beta APN in rabbits, after oral or intravenous (iv) administration. The HPLC technique was recently modified using OPA (ortho-phthalaldehyde) as the derivative agent. beta APN plasma concentration vs time following the iv administration of 200 mg/kg was best described by the biexponential equation C = 92.43.e(-0.0728 t) + 61.78.e(-0.0088 t) (t1/2 beta = 78.73 +/- 5.19 min; Vc = 1.29 +/- 0.04 L.kg-1). After oral administration, beta APN followed a zero-order absorption pattern (Ko = 3.02 +/- 0.34 mg.kg-1.min-1), which means that the beta APN reached the blood very quickly.
Sevil
M B
MB
Dpto de Toxicología y Farmacología, Universidad Complutense de Madrid, Spain.
Anadon-Baselga
M J
MJ
Frejo
M T
MT
Llama
E
E
Capo
M A
MA
D000284:Administration, Oral; D000629:Aminopropionitrile / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008657:Metabolic Clearance Rate; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors; D011817:Rabbits
D004791:Enzyme Inhibitors; D000629:Aminopropionitrile; D008249:Protein-Lysine 6-Oxidase