Effect kinetics of N-acetylprocainamide-induced QT interval prolongation.

We attempted to correlate clinical response with the effects of N-acetylprocainamide (NAPA) on the QT interval in five patients with stable chronic ventricular arrhythmias. A 15 mg/kg dose of NAPA was administered and a pharmacokinetic-pharmacodynamic model was used to relate plasma NAPA concentrations to changes in corrected QT interval (QTc). NAPA volume of distribution, elimination clearance, and elimination half-life averaged 1.37 +/- 0.19 L/kg, 174 +/- 63 ml/min, and 8.2 +/- 1.4 hours, respectively (mean +/- SD), and NAPA renal clearance averaged 1.9 +/- 0.6 times creatinine clearance. QTc prolongation was characterized by a linear-effect model in the first four patients and averaged 2.4 msec for every microgram per milliliter NAPA in a hypothetic biophase. QTc prolongation in patient 5 was exaggerated and was analyzed with an Emax model. Nonetheless, NAPA did not control this patient's arrhythmia. Conversely, patient 1 subsequently developed torsade de pointes even though QTc prolongation in this patient was comparable to that in patients 2 through 4, who responded satisfactorily to NAPA. We conclude that QT interval changes during initial NAPA administration do not reliably predict subsequent clinical response.

D-xylose absorption and disposition in patients with moderately impaired renal function.

D-Xylose kinetics were studied after oral and intravenous administration to 10 patients with impaired renal function, three of whom were being evaluated for intestinal malabsorption. The 0.32 +/- 0.06 L/kg (mean +/- SD) distribution volume of D-xylose in patients with uncomplicated renal impairment was larger than the value of 0.23 +/- 0.04 L/kg that we reported previously for normal subjects (P less than 0.01). Renal clearance was also reduced, averaging 87% of glomerular filtration rate estimated from creatinine clearance, so that the elimination-phase half-life was prolonged to 138 +/- 39 minutes from 75 +/- 11 minutes in normal individuals (P less than 0.01). The 25 gm oral D-xylose dose was 77.4% +/- 14.8% absorbed in the patients with uncomplicated renal impairment, similar to the 69.4% +/- 13.6% absorption reported in normal individuals. However, the absorption half-life was prolonged from 31 +/- 12 minutes in normal subjects to a value of 62 +/- 23 minutes (P less than 0.02). Of the usual clinical indexes of D-xylose absorption, the serum concentration measured 1 hour after the oral dose was best correlated with the extent of D-xylose absorption (r = 0.76; P less than 0.01), and the standard lower normal limit of 0.2 mg/ml was satisfactory.