Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib.

Aims: Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. The aim was to investigate whether the cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug etoricoxib affects the steady-state pharmacokinetics of digoxin.

Methods: This was a double-blind, randomized, placebo-controlled, two-period cross-over study.

Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers.

Aprepitant is the first NK1 receptor antagonist approved for use with corticosteroids and 5HT3 receptor antagonists to prevent chemotherapy-induced nausea and vomiting (CINV). The effective dose to prevent CINV is a 125-mg capsule on day 1 followed by an 80-mg capsule on days 2 and 3. Study 1 evaluated the bioavailability of the capsules and estimated the effect of food.

The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity.

To investigate the influence of modifying in vivo cytochrome P450 3A (CYP3A) activity on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, and of etoricoxib administration on CYP3A activity, a 3-part, randomized, crossover study was conducted in 3 panels of healthy volunteers. In part I, 8 subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 400 mg ketoconazole, a known strong inhibitor of CYP3A. In part II, 8 different subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 600 mg rifampin, a known strong inducer of CYP3A.

Lack of effect of aprepitant on digoxin pharmacokinetics in healthy subjects.

Aprepitant is a highly selective neurokinin-1 receptor antagonist that, in combination with a corticosteroid and a 5-hydroxytryptamine3 (5HT3) receptor antagonist, has been shown to be efficacious in the prevention of highly emetogenic chemotherapy-induced nausea and vomiting. In vitro data suggest that aprepitant is a substrate and a weak inhibitor of P-glycoprotein. Thus, the effect of aprepitant on the pharmacokinetics of digoxin, a P-glycoprotein substrate, was examined in a double-blind, placebo-controlled, randomized, two-period crossover study in 12 healthy subjects.

Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869.

Background: Recent studies have suggested that antiemetic therapy with a triple combination of the neurokinin-1 receptor antagonist MK-869, a serotonin (5-HT(3)) antagonist, and dexamethasone provides enhanced control of cisplatin-induced emesis compared with standard therapy regimens. The authors compared the antiemetic activity of a dual combination of MK-869 and dexamethasone with that of a standard dual combination of ondansetron and dexamethasone to characterize further the efficacy and tolerability profile of MK-869.

Methods: This was a multicenter, double-blind, randomized, active agent-controlled study of 177 cisplatin-naïve patients with malignant disease.