Disease relevance of NAPA

• Procainamide, NAPA and systemic lupus [1].
• A pharmacokinetic study of sodium phenylacetate/sodium benzoate (NAPA/NABZ) was performed in two groups of normal healthy volunteers, following the dosing regimen used to treat hyperammonemia [2].
• Moreover, both DMSA and DMPS are superior to BAL and NAPA in alleviating acute toxicity and in preventing the undesirable distribution of orally administered mercury, especially to the brain [3].
• A patient with chronic renal failure who experienced symptomatic ventricular tachycardia was treated successfully with procainamide (PA) after numerous dosage adjustments to optimize his clinical response and serum PA and NAPA concentrations [4].

High impact information on NAPA

• A major current issue in vesicle trafficking is whether NSF (N-ethylmaleimide-sensitive factor) and alpha-SNAP (alpha-soluble NSF attachment protein) are required prior to SNARE (SNAP receptor) complex formation to allow vesicle docking, or after docking at a step close to membrane fusion [5].
• Immunoprecipitation of NAPA-insulin-stimulated cells with anti-phosphotyrosine antibodies revealed that 62% of the processed labeled receptors, but very little proreceptor, contained phosphotyrosine [6].
• The steady-state pharmacokinetics and pharmacodynamics of procainamide and its active N-acetyl metabolite (NAPA) were assessed alone and in combination with trimethoprim [7].
• The change in procainamide and NAPA renal clearances after trimethoprim coadministration strongly correlated with their baseline renal clearances (r = 0.84 and r = 0.74, respectively, p less than 0.0001) [7].
• The apparent dependence of this effect on underlying status of left ventricular function suggests that the initial reduction in PEP/LVET represents an an indirect effect of NAPA rather than a direct inotropic action [8].

Chemical compound and disease context of NAPA

• According to the antagonistic effects noted on mortality, peristaltic toxicity and intestinal cadmium uptake, the relative efficacies of the compounds tested were: DMSA greater than PAD greater than DMPS greater than MSA greater than PA greater than NAPA [9].

Biological context of NAPA

• NAPA pharmacokinetics were studied in 6 functionally anephric patients [10].
• Despite this marked variation, there were no significant changes in PCA renal clearance or 24-hr PCA or NAPA excretion [11].
• Significant changes of AUC and renal clearance of the active metabolite--N-acetylprocainamide (NAPA) were found only following the dose of 400 mg cimetidine [12].
• Intravenous NAPA is a relatively weak peripheral arterial and venous dilator which reduces cardiac output producing a reflex increase in the heart rate [13].
• The hemodynamic effects of the class III antiarrhythmic agent N-acetylprocainamide or NAPA were assessed in 14 patients with preserved ventricular function undergoing cardiac catheterization [13].

Anatomical context of NAPA

• Dialysis removed NAPA from both red blood cells and plasma and increased ClT approximately fourfold [10].

Associations of NAPA with chemical compounds

• Placebo period PVC frequency after one year of NAPA therapy was reduced, compared to baseline placebo values [8].
• The effect of ranitidine on the disposition of procainamide and NAPA was evaluated in 13 healthy men [14].
• We present a method for the analysis of antidysrhythmic drugs [procainamide, acecainide (NAPA), lidocaine, quinidine, disopyramide, N-desisopropyl disopyramide, and propranolol] in serum [15].
• Free NAPA levels in the blood of dogs receiving PHT were found to be considerably high, whereas free SAM levels in the blood of dogs receiving ETB were very low [16].
• The larger dose of cimetidine produced greater alteration in the PA and NAPA pharmacokinetics [12].

Other interactions of NAPA

• Both syntaxins are found in SNARE complexes that are dissociated by alpha-soluble NSF attachment protein and NSF [17].

Analytical, diagnostic and therapeutic context of NAPA

• Serum concentrations and urinary excretion rates of PA and its active metabolite, NAPA, were measured by high performance liquid chromatography [18].
• Comparative studies on the disposition of two pairs of drugs and their prodrugs, i.e., (1) salicylamide (SAM) and ethenzamide (ETB), (2) acetaminophen (NAPA) and phenacetin (PHT), were performed in dogs following intravenous and oral administration of the drugs [16].
• These results were then used to estimated flow-intercompartmental clearance relationships for PA and NAPA and to predict the extent of hemodynamic changes causing the slow intercompartmental clearance of NAPA to decrease by 77% during hemodialysis without an apparent alteration in fast intercompartmental clearance [19].

References