Background: Intramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. Concerns exist regarding implications of epinephrine auto-injector needles not penetrating the muscle in patients with greater skin-to-muscle-distances (STMD). Methods: This open-label, randomized, crossover study investigated pharmacokinetics and pharmacodynamics following injection of epinephrine in healthy volunteers. Individuals were stratified by maximally compressed STMD (low, < 15 mm; moderate, 15-20 mm; high, > 20 mm). Participants received epinephrine injections via EpiPen ® Auto-Injector (EpiPen; 0.3 mg/0.3 mL) or IM syringe (0.3 mg/0.3 mL) at mid-AL thigh or received saline by IM syringe in a randomized order. Eligible participants received a fourth treatment (EpiPen [0.3 mg/0.3 mL] at distal-AL thigh). Modelindependent pharmacokinetic parameters and pharmacodynamics were assessed. Results: There were numerical trends toward higher peak epinephrine concentrations (0.52 vs 0.35 ng/mL; geometric mean ratio, 1.40; 90% CI 117.6-164.6%) and more rapid exposure (time to peak concentration, 20 vs 50 min) for EpiPen vs IM syringe at mid-AL thigh across STMD groups. Absorption was faster over the first 30 min for EpiPen vs IM syringe (partial area under curve [AUC] over first 30 min: geometric mean ratio, 2.13; 90% CI 159.0-285.0%). Overall exposure based on AUC to the last measurable concentration was similar for EpiPen vs IM syringe (geometric mean ratio, 1.13; 90% CI 98.8-129.8%). Epinephrine pharmacokinetics after EpiPen injection were similar across STMD groups. Treatments were well tolerated. Conclusions: Epinephrine delivery via EpiPen resulted in greater early systemic exposure to epinephrine vs IM syringe as assessed by epinephrine plasma levels. Delivery via EpiPen was consistent across participants with a wide range of STMD, even when the needle may not have penetrated the muscle.

MYL-1401H demonstrated similar PK, PD, and safety to reference pegfilgrastim in healthy volunteers and may be an equivalent option for the prevention of febrile neutropenia.

MYL-1401O was well tolerated and demonstrated PK and safety profiles similar to EU-trastuzumab and US-trastuzumab in healthy volunteers (ClinicalTrials.gov, NCT02594761).

Background Nebivolol (N) has been shown through a number of studies to be a cardioselective β1‐antagonist with vascular endothelial nitric oxide releasing capabilities that exhibits CYP2D6‐mediated polymorphic metabolism. Losartan (L), an ARB, is extensively metabolized by CYP2C9 (a known polymorphic enzyme) and is likely to be used concomitantly. This study examined if co‐administration of N and L alters the pharmacokinetic (PK) characteristics of either agent, or the active metabolite of L, EXP‐3174. Methods This open‐label study was conducted in 24 subjects, genotyped for CYP2D6 status (EM n=20; PM n=4). Using a two‐sequence, two‐treatment design, single doses of 10 mg N (Day 1 or 29), 50 mg L (Day 1 or 29), or their combination (Day 15) were given. Blood samples for PK assessment were taken on Days 1, 15 and 29. Results (see Table) Conclusion There were no clinically meaningful changes observed in the PK of either L or N, confirming that the two agents should be capable of being safely co‐administered. Clinical Pharmacology & Therapeutics (2005) 77, P82–P82; doi: Cmax AUC0‐∞ Parameter Ratio 90% CI Ratio 90% CI EM‐N0.800.68–0.930.890.82–0.97PM‐N0.930.76–1.140.940.68–1.29L0.890.77–1.020.860.81–0.92EXP‐31740.940.86–1.030.980.94–1.02

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