Fosaprepitant is an intravenous formulation of aprepitant, an oral NK1 antagonist used to prevent chemotherapy-induced nausea and vomiting. This randomized study was designed to evaluate fosaprepitant in polysorbate 80 vehicle for tolerability and bioequivalency to aprepitant. Tolerability was assessed by physical and laboratory examinations and adverse events. Plasma collected for 72 hours was assayed for aprepitant and fosaprepitant. Analysis of variance models were applied to natural log-transformed aprepitant area under the curve (AUC) data. Fosaprepitant up to 150 mg (1 mg/mL) was generally well tolerated. Fosaprepitant 115 mg was AUC bioequivalent to aprepitant 125 mg; the 90% confidence interval for the geometric mean ratio of aprepitant AUC for fosaprepitant 115 mg/aprepitant 125 mg fell within prespecified equivalence bounds of 0.80 to 1.25.

These studies provide evidence of limited glucose lowering and incretin activity for JNJ-38431055 in subjects with T2DM.

The incidence of type 2 diabetes mellitus is increasing worldwide. Several G-protein-coupled receptor agonists are being studied for their efficacy as antidiabetes agents. JNJ-38431055 is a novel, potent, and orally available selective agonist of the glucose-dependent insulinotropic (GPR119) receptor. Double-blind, randomized, placebo-controlled studies were conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of JNJ-38431055 (2.5-800 mg) in healthy male volunteers. The systemic exposure of JNJ-38431055 in plasma increased in proportion to the dose and was not influenced by coadministration of food. The terminal elimination half-life was ~13 h when administered as an oral suspension formulation. JNJ-38431055 was well tolerated and was not associated with hypoglycemia. As compared with placebo, single-dose oral JNJ-38431055 increased postmeal plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations but did not significantly decrease glucose excursion or increase insulin secretion. However, in a graded glucose infusion study, JNJ-38431055 was shown to induce a higher insulin secretion rate (ISR) relative to placebo at elevated plasma glucose levels. These studies provide evidence for the potential efficacy of JNJ-38431055 as an antidiabetes agent in humans.

As the aprepitant antiemetic regimen has no detectable inhibitory or inductive effect on the pharmacokinetics of vinorelbine, aprepitant when added to a standard antiemetic regimen consisting of ondansetron and dexamethasone can be safely combined with vinorelbine at clinically recommended doses.

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Bioequivalence of ezetimibe/simvastatin tab let and coadministrationAb stract. Ob jec tive: To as sess the bioequivalence of an ezetimibe/simvastatin (EZE/SIMVA) com bi na tion tab let in com pari son with the coadministration of eze timibe and simvastatin as sep a rate tab lets (EZE + SIMVA). Meth ods: In this open-la bel, random ized, 2-part, 2-pe riod cross over study, 96 healthy sub jects were ran domly as signed to par tic i pate in each part of the study (Part I or II), with each part con sist ing of 2 sin gle-dose treat ment pe ri ods sep a rated by a 14-day wash out. Part I con sisted of Treat ments A (EZE 10 mg + SIMVA 10 mg) and B (EZE/SIMVA 10/10 mg/mg) and Part II consisted of Treat ments C (EZE 10 mg + SIMVA 80 mg) and D (EZE/SIMVA 10/80 mg/mg). Blood sam ples were col lected up to 96 hours post-dose for de ter mi na tion of ezetimibe, total ezetimibe (ezetimibe + ezetimibe glucuron ide), simvastatin and simvastatin acid (the most prev a lent ac tive me tab o lite of sim vastatin) con cen tra tions. Ezetimibe and sim vastatin acid AUC (0-last) were pre de fined as primary end points and ezetimibe and sim vastatin acid C max were sec ond ary end points. Bioequivalence was achieved if 90% con fidence in ter vals (CI) for the geo met ric mean ra tios (GMR) (sin gle tab let/coad min is tration) of AUC (0-last) and C max fell within prespecified bounds of (0.80, 1.25). Re sults: The GMRs of the AUC (0-last) and C max for ezetimibe and simvastatin acid fell within the bioequivalence lim its (0.80, 1.25). EZE/ SIMVA and EZE + SIMVA were gen er ally well tol er ated. Con clu sions: The low est and high est dos age strengths of EZE/SIMVA tablet were bioequivalent to the in di vid ual drug com po nents ad min is tered to gether. Given the ex act weight mul ti ples of the EZE/SIMVA tab let and lin ear pharmacokinetics of simvastatin across the mar keted dose range, bioequivalence of the in ter me di ate tab let strengths (EZE/SIMVA 10/20 mg/mg and EZE/SIMVA 10/40 mg/mg) can be ex pected, al though these dos ages were not tested directly. These re sults in di cate that the safety and ef fi cacy pro file of EZE + SIMVA coadmi nis tration ther apy can be ap plied to treatment with the EZE/SIMVA tab let across the clin i cal dose range.

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