4‐Aminopyridine kinetics

Nine healthy subjects (7 men; 2 women) received single 20‐mg IV injections of 4‐aminopyridine (4‐AP). Six of the subjects received the same dose in the form of enteric‐coated tablets and four the same dose in uncoated tablets; treatments were at least 2 wk apart. Blood, saliva, and urine were assayed for 4‐AP using a high‐performance liquid chromatography. Kinetic analysis of serum concentrations after intravenous dosing resulted in the best fitting of a triexponential model in five and a biexponential model in four subjects. The apparent volume of distribution (V) was 2.6 ± 0.9 (mean ± SD) l/kg −1 , the terminal half‐life (t½) 3.6 ± 0.9 hr, and the total serum clearance 0.61 ± 0.14 lhr −1 kg −1 . Saliva concentrations were higher than those in serum after 5 min, with a mean correlation coefficient of 0.989 (n = 5). The t½ and V calculated from serum and saliva concentrations were of the same order. The total urinary excretion of unchanged 4‐AP was 90.6 ± 7.8% after intravenous doses and 88.5 ± 4.8% after oral doses of enteric‐coated tablets. The bioavailability of the enteric‐coated tablets calculated from the area under the serum concentration curve (95 ± 29%) did not differ from that calculated from urinary excretion (98 ± 8%). Protein binding of 4‐AP was found to be negligible. Biotransformation is unlikely. Clinical Pharmacology and Therapeutics (1982) 31, 587–593; doi: 10.1038/clpt.1982.82