Blood Plasma Levels and Elimination of Salts of 2-Pam in Man after Oral Administration

摘要

Adult male volunteers were given, orally, aqueous solutions of each of the chloride, iodide, dihydrogen phosphate, methane sulfonate, and lactate salts of 2-PAM in varying amounts. A measurable amount of oxime was found in blood plasma within about 15 minutes; the concentration rose rapidly, reached a peak at 2 to 3 hours, and then declined at a rate that approximated a first-order process. The rates of absorption into and elimination from plasma of 2-PAMCl and P2S were practically identical. The equation, log Y = 0.79 + 0.54 log X, gives an approximate relationship between peak plasma levels of oxime (Y) and oral doses (X) of the various salts. Accordingly, a 10-fold increase in dosage of the 2-PAM salts increased the peak plasma level of oxime 3.5 fold. The biological half-life in man of the 2-PAM salts given orally, calculated from blood plasma values and urinary excretion rates, was 1.7 hours, with a coefficient of variation of 24%. The average total amount of 2-PAM recovered in the urine was 27%; the standard deviation of individual recoveries was 9%. Considerably less EA 1814 is excreted via the urine; an average of 3% was recovered during 24 hours among three subjects. Clinical changes observed were: (1) iodism symptoms in subjects given 2-PAM and (2) a 20% decrease in both RBC and plasma cholinesterase in subjects given 1 gm/70 kg of EA 1814. All other clinical tests were negative. (Author)