Our results show that intracellular etravirine levels were similar with both dosing regimens in patients with PI-sparing regimens, while etravirine plasma AUC(0-τ) and C(max) were 30% and 76% higher with the once-daily regimen, respectively. Thus, a once-daily dosing regimen is supported not only by plasma etravirine pharmacokinetic profiles but also by intracellular levels.
There is a pharmacokinetic interaction between digoxin and diazepam that increases the elimination half-life of digoxin. It may be due to a reduction of digoxin tissue concentrations and to an enhanced effect of diazepam on digoxin binding to plasma albumin. Diazepam (10(-5) M) also induces a positive inotropic effect in guinea-pig isolated atria. In a study of a possible pharmacodynamic interaction between both drugs, the inotropic response to digoxin has been examined in rat isolated atria in the presence of diazepam. The atria were kept in Tyrode at 37 degrees C, bubbled with 95% O2 and 5% CO2 and electrically stimulated at twice the threshold voltage. The results indicate that diazepam induces an inotropic effect at 10(-5) M (P less than 0.05) and reduces (P less than 0.05) at 10(-9), 10(-7) and 10(-5) M the inotropic response to digoxin (10(-5) M).
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