PHARMACOKINETIC ANALYSIS OF BETA-AMINOPROPIONITRILE IN RABBITS

beta-Aminopropionitrile (beta APN), inhibits the activity of lysyl oxi dase, an important enzyme for the post-translational formation of inte r- and intramolecular covalent cross-linking between the connective ti ssue proteins, collagen and elastin. We became interested in the possi ble use of this compound as a therapeutic agent in the so-called human collagen diseases. beta APN's action mechanism is known, but its phar macokinetics in rabbits have not yet been determined. The present stud y defined the kinetic parameters of beta APN in rabbits, after oral or intravenous (iv) administration. The HPLC technique was recently modi fied using OPA (ortho-phthalaldehyde) as the derivative agent. beta AP N 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) (t(1/2 beta) = 78.73 +/- 5.19 min; V- c = 1.29 +/- 0.04 L . kg(-1)). After oral administration, beta APN fol lowed a zero-order absorption pattern (K-o = 3.02 +/- 0.34 mg.kg(-1).m in(-1)), which means that the beta APN reached the blood very quickly.