Following single or multiple nebulized-dose administration in patients with COPD, revefenacin demonstrates a rapid onset and sustained duration of bronchodilator effect over 24 h following once-daily administration, with a PK profile that is commensurate with low systemic exposure.

In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients with symptomatic CHF and anemia (hemoglobin

Palifermin exhibited linear pharmacokinetics and caused dose-dependent epithelial proliferation.

Background/Aims PAL has been shown in hematological cancer patients to reduce the duration, incidence, and severity of mucositis following 3‐consecutive daily doses of 60 ug/kg. In the studies described here, the PK/PD of PAL was evaluated. Methods In 2, randomized, double‐blind, placebo‐controlled, dose escalation studies, healthy subjects received single (SL) (60–250 ug/kg) or multiple (MP) (40 ug/kg/day[d] × 3d) IV doses of PAL or placebo. PK and PD (Ki67 staining on buccal mucosa biopsies) assessments were conducted at baseline and postdose. Results 75 subjects (18–63 yrs) received PAL. Exposure to PAL increased approximately dose proportionally (3‐fold increase in C0 and AUC for a 4‐fold increase in dose). An increased PD response was observed with increased dose, with an apparent flattening of the dose response relationship at higher doses. The PD response 24 hrs after the 3rd MP dose of 40 ug/kg was similar to that at 48 hrs after a SL dose of 120 ug/kg. Conclusions A SL collapsed dose yields comparable PD to the same total dose partitioned over 3 consecutive days. Based on the safety, PD, and efficacy profiles of PAL, future oncology trials will be conducted using a SL 180 ug/kg dose in lieu of 3 doses at 60 ug/kg. Clinical Pharmacology & Therapeutics (2005) 77, P17–P17; doi:

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8622 Background: Zensana ondansetron oral spray (ZSN) is the first oral spray 5-HT3 antagonist to deliver ondansetron, the most commonly prescribed anti-emetic for chemotherapy induced nausea and vomiting (CINV) through the oral cavity. ZSN achieves therapeutic drug levels by delivering small droplets of concentrated drug solution over the oral mucosa, which has a rich blood supply and has been shown to be an alternative drug delivery route. ZSN may offer certain advantages to patients experiencing CINV who have difficulty swallowing and holding down pills. Methods: This was a randomized, crossover, pharmacokinetic (PK) study where ZSN, administered as 4mg, 8mg, 12mg, and 8mg with a 30-sec hold before swallowing was evaluated in healthy subjects against an 8mg ondasetron (Zofran [ZFR]) tablet (reference). Treatments were separated by 48 hrs. PK samples were measured during the 24 hrs after dosing and were assayed using LC/MS/MS techniques. PK parameters were analyzed using a cross-over ANOVA model. Two treatments were concluded bioequivalent if the 90% CI of the geometric mean ratios for ln-transformed Cmax, AUC0-t, and AUC0-inf fell between the FDA guideline of 80% to 125%. Results: Thirty-two subjects (17 women, 15 men) received each of the 5 treatments, except for one man who did not receive the 12mg dose. The geometric mean ratios and the 90% CI for Cmax, AUC0-t, and AUC0-inf respectively, for each pair of treatments were as follows: ZSN 4mg vs 8mg tablet (TAB): 41%(39–43%); 45%(43–47%), and 47%(45–49%); ZSN 8mg vs 8mg TAB: 87%(83–91%), 98%(94–102%), and 99%(94–103%); ZSN 12mg vs 8mg TAB: 145%(138–152%), 157%(150–164%), and 157%(150–164%); and ZSN 8mg with a 30 sec hold vs 8mg TAB: 86%(82–90%), 99%(94–103%), and 99%(95–104%). There were no serious or unexpected adverse events (AE) and the safety profile was similar across all treatments. The most commonly reported AEs were constipation (11/32[34%]), headache (10/32[31%]), and dizziness (5/32[16%]) which were mild to moderate in severity. Conclusions: ZSN 8mg falls within the FDA criteria for bioequivalence, and is bioequivalent to an 8mg ZFR tablet. ZSN 4, 8, or 12mg has a similar safety profile as a ZFR 8 mg tablet. [Table: see text]