CHOLINE PHARMACOKINETICS DURING INTERMITTENT INTRAVENOUS CHOLINE INFUSION IN HUMAN-SUBJECTS

A study of choline pharmacokinetics was undertaken in four patients re ceiving long-term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol choline chloride were intravenously infused over a 12-hour period in each subject. The choline concentration was determi ned in plasma at baseline, 1/4, 1, 3, 6, and 12 hours, and 3 and 12 ho urs after the infusion ended, and in daily 24-hour urine collections. Analysis of variance showed the data fit a two-compartment model in wh ich elimination from the central compartment was saturable significant ly better than a one-compartment model in all four subjects (p < 10(-8 ) in all cases), and significantly better than a nonsaturating model i n three of the four subjects (p = 1.0 x 10(-9), 7.5 x 10(-6), 9.4 x 10 (-11), respectively). The model allowed estimates of the rate constant for choline elimination at ambient levels, first-order rate constants for transfer between central and peripheral compartments, the dissoci ation constant for the saturable elimination process, the apparent vol ume of distribution in the central compartment, the steady-state volum e of distribution, and the quantities of choline in the central compar tment and in the readily exchangeable pool.