Spectrophotometric, kinetic, and nuclear magnetic resonance studies indicate that alkaline sodium picrate and creatinine react to form a 1/1 aduct between picric and creatinine, with a stability constant of log K= 4.26. Kinetic studies indicate that the forward reaction is first order with respect to picric acid, hydroxide, and creatinine concentration. The reverse reaction, the dissociation of the 1/1 complex, shows a complex dependence on hydroxide concentration. The expression for the observed pseudo-first-order rate constant in the presence of excess picric acid is: Kobsd = K1K0[P][OH] +[K2[OH]x. A value of K1K0 = 5.0 (mol/liter)-2s-1 is obtained. For accurate analytical results with this reaction, hydroxide concentration must be maintained at a constant value for both samples and standards.

The antifibrillatory properties of short-term intravenous (10 mg/kg/hr) and long-term (10 mg/kg/day for 24 days) oral amiodarone administration were examined in a conscious canine preparation of sudden coronary death. In this preparation, ventricular fibrillation was produced by electrically induced left circumflex intimal injury and thrombosis in the presence of previous anterior myocardial infarction. On day 4 after anterior myocardial infarction animals were assigned to receive short-term intravenous or long-term oral amiodarone treatment. Animals within each group were randomly assigned to control or drug treatment. Neither short-term intravenous nor long-term oral amiodarone treatment prevented the development of ST segment changes or premature ventricular beats, but both short-term intravenous amiodarone and long-term oral amiodarone administration significantly reduced the incidence of ventricular fibrillation (short-term intravenous amiodarone [n = 10], incidence of 60% vs control [n = 10] incidence of 100%, p < .05; long-term oral amiodarone [n = 10], incidence of 20% vs control [n = 11] incidence of 91%, p < .002). Both short-term intravenous and long-term oral amiodarone administration produced increases in the PR and ratecorrected QT intervals. However, prolongation of the corrected QT interval in the group receiving long-term oral amiodarone (61 + 18 msec) was greater than in the group receiving short-term intravenous drug (31 ± 11 msec, p < .05). This discrepancy between effects of long-term oral and short-term intravenous amiodarone could not be based on differences in plasma (1.9 0.2 vs 2.7 + 0.5 gg/ml, respectively) or right ventricular myocardial concentrations (13 + 2 vs 24 + 4 ,g/g, respectively). These data suggest that while both long-term oral amiodarone and short-term intravenous amiodarone prevent ventricular fibrillation in the conscious dog subjected to acute myocardial ischemia in the presence of previous anterior myocardial infarction, long-term oral amiodarone may have an additional electrophysiologic action and therefore greater efficacy.Circulation 68, No. 4, 857-864, 1983. AMIODARONE HYDROCHLORIDE is a benzofuran derivative originally developed as an antianginal drug. It is both a coronary vasodilator and a vasodilator of the peripheral vasculature.'-3 Amiodarone also exerts noncompetitive blockade of the actions of 38-adrenergic agonists and reduces the inotropic and chronotropic response of other inotropic drugs such as glucagon.

With data on adults from two previous articles it was found that the average steady-state plasma concentration of verapamil in subjects on long-term oral therapy of 80 mg every 6 hr (Y) correlated strongly with the area under the curve from zero to infinity (AUC0-x/6 (X) where the area refers to that for a single oral dose of 80 mg (Y - 2.41X, n - 15, r - 0.923, P less than 0.001). Steady-state concentrations are predictable from the single-dose data, with an average absolute deviation of 11.1%. We gave seven children (7 to 19 yr old) an initial intravenous bolus dose of 0.1 mg/kg, followed by a 20-min constant rate infusion of 0.007 mg/kg/min. Twenty-four hours after the bolus dose they were put on oral therapy (40 to 80 mg every 6 hr) and 1 mo later the minimum steady-state verapamil plasma concentration (Cminss) was measured. Plasma concentration-time data obtained after the infusion were fitted to biexponential (two sets) or triexponential equations (five sets). The coefficients of the postinfusion polyexponential equations were converted to those for the 0.1-mg/kg bolus dose alone. Mean parameters estimated were: plasma clearance 0.500 l/min, steady-state volume of distribution 279 l, V beta 394 l, half-life 9.17 hr, and mean residence time 10.0 hr. Many correlations were made between the oral Cminss values and functions obtained from the intravenous data. The best correlation was that between Cminss and the predicted steady-state concentration at 3 hr after dosing when bolus doses would be given at 6-hr intervals based on the single-dose intravenous date (r = 0.985, P less than 0.001); this correlation allowed Cminss to be predicted with an average absolute deviation of 10%. Norverapamil was measured in plasma after oral dosing, but was not detectable after intravenous dosing.

0.27, respectively. The influence of some products of degradation of NTA and some chemical species expected to be present in natural and industrial waters was also investigated. Iminodiacetic acid, glycolic acid, glycine, dodecylbenzene sodium sulfonate, sodium tripolyphosphate, and calcium ion did not interfere at least in molar concentrations 100 times that of NTA. Ortho-and m-cresol, and iron(II1) ion did not interfere if present at the same molar level of NTA. Aluminum ion and sodium lauryl sulfate can be tolerated in molar concentrations 10 times that of NTA. Dissolved chlorine proved to be the only serious interference of all species considered. Figure 3 presents a working curve for NTA with a known constant amount of EDTA. This figure implies that by adding the adequate amount of Mn(I1) and selecting appropriate reference potentials, the procedure can be used for the determination of NTA in samples of aminopolycirboxylic acids (or other complexing agents) inhibiting the catalytic effect of manganese (i.e,, CDTA, DTPA, EDTA, and HEDTA). Aminopolycarboxylic acids2 are detected and determined, individually or in mixtures, by the reaction of cyanide ion with their nickel(l1) complexes in basicsolution. The procedure is based on the large differences in the rate of formation of tetracyanonickelate ion. Simultaneous kinetic determinations of twocomponent (NTA and EDDA) and three-component (NTA, EDDA, and EGTA) mixtures are accomplished by on-line regression analysis of stopped-flow spectrophotometric data. As little as 10 ppb of NTA in natural water samples can be detected. Trace amounts of NTA in EDTA and a four-component (EGTA, HPDTA, HEEDTA, and EDTA) mixture also are determined offline.

SUMMARY The acute hemodynamic effects of verapamil were evaluated in nine children with hypertrophic cardiomyopathy. Verapamil, 0.1 mg/kg, was administered as an i.v. bolus over 2 minutes, followed by a 20-minute continuous infusion of 0.007 mg/kg/min. Hemodynamic measurements were obtained at rest in nine patients and at maximal supine bicycle exercise in seven before and 15 minutes after verapamil. At rest, verapamil increased the mean cardiac output from 3.3 0.9 to 3.7 0.9 1/min/m2 (± SD) (p < 0.02) and decreased left ventricular end-diastolic pressure from 19.3 ± 8.1 to 14.5 ± 6.9 mm Hg (p < 0.006). In six patients with resting left ventricular outflow tract obstruction, the systolic pressure gradient decreased from 17.5 ± 7.2 to 5.2 ± 4.5 mm Hg (p < 0.04). Repeat supine bicycle exercise testing after verapamil showed increases in total work performed (1743 ± 1284 to 3168 + 1643 kg-m, p < 0.006) and maximal cardiac index during exercise (6.5 ± 1.3 to 7.8 ± 1.8 I/min/m2, p < 0.05), and decreases in maximal exercise left ventricular end-diastolic pressure (29