George B. Park

Dose proportionality of amrinone

Arminone was given to 18 healthy subjects in doses of 75, 150, and 225 mg in a randomized crossover design. Plasma levels were shown to rise in proportion to dose. The mean plasma AUC, extrapolated to infinite time, was determined for each dose level; the values obtained were 4, 8.18, and 12.35 μg · hr/ml for the 75‐, 150‐, and 225‐mg doses. Mean maximum observed plasma concentrations were 1.03, 1.74, and 2.58 μg/ml. At higher doses the extrapolated AUC is more variable, but it is linear over the range of 0.73 to 3.81 mg/kg. The apparent first‐order terminal elimination rate is not dose dependent and corresponds to a t½ of 3.85 hr.

The analysis of arildone in plasma, urine and feces by gas—liquid chromatography with electron-capture detection

The analysis of arildone in plasma, urine and feces by gas--liquid chromatography with electron-capture detection is described. O-(2,3,4,5,6-Pentafluorobenzyl)hydroxylamine is the derivatizing agent for the plasma and urine analysis; 3-nitrophenylhydrazine is utilized for fecal analysis. The mean (+/- S.E.) minimum quantifiable level of arildone was 1.4 (+/- .02) ng/ml in urine, 6.4 (+/- 0.1) ng/ml in plasma, and 12.6 (+/- 1.0) ng/g in feces. The chromatographic response was linear in the range of 0 and 10--120 ng/ml for plasma, 0 and 2.5--20 ng/ml for urine and 0 and 25-250 ng/g for feces. The estimated overall precision of the assay was 5.5%, 64% and 8.9% in urine, plasma and feces, respectively.