A third, "deep," compartment for phenothiazine drug disposition: a new look at an old problem

Volunteers were given oral promazine doses, and blood and urine were collected for promazine assay for as long as was necessary for the drug to cease to be detectable. Postabsorption data were subjected to two- and three-compartment modeling. Renal clearance was calculated. Renal excretion data were analyzed by use of the sigma-minus method, which permits the calculation of the half-life in plasma from excretion data. The mean alpha-phase rate constant for plasma decay (plasma assays) was .0155 min-1. The mean beta-phase rate constant for plasma decay (plasma assays) was .0046 min-1; the mean beta-phase rate constant for plasma decay (urine assays) was .0056 min-1. The mean gamma-phase rate constant for plasma decay (urine assays) was .00075 min-1. These data demonstrate the existence of a third, deep, distribution compartment from which promazine is released slowly and which is only detectable by means of excretion studies.