4-Aminopyridine kinetics

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Abstract
4-Aminopyridine (4-AP) is used as an antagonist of the neuromuscular blockade induced by curariform drugs. Nine healthy subjects (7 men, 2 women) received single 20-mg i.v. injections of 4-AP. Of the subjects, 6 received the same dose in the form of enteric-coated tablets and 4 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 i.v. dosing resulted in the best fitting of a triexponential model in 5 and a bioexponential model in 4 subjects. The apparent volume of distribution (V) was 2.6 .+-. 0.9 (mean .+-. SD) l/kg, the terminal half-life (t1/2) 3.6 .+-. 0.9 h, and the total serum clearance 0.61 .+-. .+-. 0.14 l/h per kg. Saliva concentrations were higher than those in serum after 5 min, with a mean r of 0.989 (n = 5). The t1/2 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 i.v. 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 negligible and biotransformation was unlikely.