Famotidine increases plasma alcohol concentration in healthy subjects

The effect of famotidine on plasma alcohol concentration was studied in 24 healthy male subjects who demonstrated high apparent ethanol first-pass metabolism after oral (p.o.) and intravenous (i.v.) ethanol administration (i.e. AUC_po S 40% of AUC_iv, where AUC is area under the plasma ethanol concentration-time curve). Six of the original 30 subjects screened (20%) did not demonstrate high first-pass metabolism and were excluded. In a randomized open crossover study, oral ethanol pharmacokinetics were assessed after breakfast in the morning following a 3-day regimen of famotidine, 40 mg/day, and following a no-drug control period. Famotidine increased the area under the plasma ethanol concentration-time curve (AUC_0-t) by 29% (7.1 vs 5.5 mg.h/dL, P= 0.006) and maximal plasma concentration (C_max) by 23% (9.2 vs 7.5 mg/dL, P= 0.013). The changes in ethanol AUC_0-t and C_max may have been associated with changes in gastric emptying, as they were inversely correlated with changes in the time at which maximal plasma concentration was attained. There was considerable intra-individual variation in ethanol AUC and C_max. As a result, regression to the mean is a potentially confounding problem in ethanol pharmacokinetic studies when subjects are selected on the basis of having low AUC_po, and properly controlled randomized studies of substantial size are required to detect modest drug effects. Small effects on ethanol pharmacokinetics have now been demonstrated with all four of the major H₂-receptor antagonists, but these effects are seen only under specific experimental conditions and appear to be unimportant clinically.     

Solubility of enamel powder following treatments with 1% sodium dodecyl sulphate in the presence and absence of fluoride

Deionized water exerts a solubility effect on enamel which is increased in the presence of sodium dodecyl sulphate (SDS), at a concentration used in dentifrices. As expected, incorporation of fluoride by enamel decreases the solubility effect of the detergent in water and acidic buffer. With duration of treatment, the detergent has a lesser effect than demineralized water alone on subsequent solubility of enamel in acidic buffer.     

Stability of the Defibrillation Probability Curve with the Development of Ventricular Dysfunction in the Canine Rapid Paced Model

Most patients with implantable defibrillators have diminished cardiac function. Progressive heart failure might impair defibrillation efficacy, leading to interpreted device, failure. This study sought to determine the effect of ventricular dysfunction on defibrillation energy using a biphasic endocardial system. Eleven dogs were ventricularly paced at 225 pulses/min for 2 weeks to induce ventricular dysfunction, and five control dogs remained unpaced. Dose response defibrillation probability curves were generated for each animal at baseline, after 2 weeks (at which time the pacemakers were turned off in the paced group), and then 1 week later. The defibrillation thresholds, ED₂₀, ED₅₀, and ED₈₀ (the 20%, 50%, and 80% effective defibrillation energies, respectively) were determined for each dog at each study. In the paced dogs, the mean ejection fraction fell from 55% to 25% after pacing (P < 0.0001), and rose to 46% after its discontinuation (P = 0.0002). The defibrillation threshold, ED20, ED₅₀, and ED80 remained unchanged in both the control and paced groups for all three studies, even after adjustment for dog weight or left ventricular mass. Rapid pacing produced no change in left ventricular mass. It induced ventricular cavity dilatation and wall thinning, which had opposing effects on defibrillation energy requirements, resulting in no net change of the ED₅₀ in heart failure. In conclusion, the defibrillation efficacy of a biphasic transvenous system is not changed by the development of heart failure using the rapid paced canine model.