Single-Dose Pharmacokinetics and Safety Pharmacodynamics of Formoterol Delivered by Two Different Dry Powder Inhalers
ABSTRACT The present study aimed at assessing the pharmacokinetics (PK) and safety pharmacodynamics (PD) of 24 microg formoterol delivered via a Novolizer and via an Aerolizer in healthy subjects. This was a randomized, open-label, crossover study. Beside PK, serum potassium, and glucose profiles, vital signs, and ECG were recorded. Twenty-nine subjects (15 males) were enrolled. The inhalation maneuver had to be repeated by 19 subjects using the Aerolizer and 1 subject using a Novolizer. While eight (28%) subjects completely failed to inhale correctly via the Aerolizer (four were identified by the investigators immediately after inhalation, another four by bioanalytics later), all did it correctly via the Novolizer. The bioanalytical evaluation indicated two distinct serum peaks. The shapes of serum concentration-time profiles were more homogeneous after inhaling via the Novolizer than via the Aerolizer. After adjusting for the delivered dose the Cmax of formoterol predicting pulmonary absorption was higher after the Novolizer than after the Aerolizer, while the average AUC0-infinity levels indicating total systemic exposure were equivalent. There was no evidence for different pharmacodynamic behavior with respect to serum potassium and glucose profiles, vital signs, and ECG. The Novolizer yields higher pulmonary absorption of formoterol than the Aerolizer and equivalent safety profiles. Considering the lower variability of PK profiles and the higher proportion of correct inhalations, formoterol is more reliably inhaled via Novolizer.
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ABSTRACT: Enhanced therapeutics are drug products derived from existing generic drugs that provide additional benefits to the patients and the healthcare system. Enhanced therapeutics are considered to be an important and relatively low risk source of innovation. Pulmonary drug delivery is the major delivery route to treat chronic respiratory diseases and has been proven as a potential delivery route for complex drugs that cannot be delivered orally. Development of dry powder inhalation systems targets the delivery of fine drug particles to the deep lung surface by a combination of drug formulation, primary packaging and a device, whereby each contributes to the overall performance. Various methodologies for the non-clinical and clinical performance testing of orally inhaled products have been proposed and applied with variable success. Regulatory pathways have been developed and applied since. Considerable efforts have been made during the past decade to understand and optimize pulmonary drug delivery including their efficient commercial manufacturing. Pulmonary drug delivery remains an area of future innovation in the effective treatment of pulmonary diseases as well as the systemic delivery of systemically active complex drugs.European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2012; 48(1-2). DOI:10.1016/j.ejps.2012.10.021 · 3.35 Impact Factor
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ABSTRACT: The use of formoterol in sports is allowed by inhalation at the maximum recommended therapeutic dose. Recently, a threshold concentration of 30 ng.mL(-1) was defined by the World Anti-Doping Agency (WADA) to distinguish between therapeutic and forbidden use of formoterol. The objective of this work was to evaluate that threshold concentration. Concentrations of formoterol were measured in urine samples collected after administration of 18 µg of inhaled formoterol to five healthy volunteers, and in samples collected in routine doping tests belonging to athletes having declared inhaled formoterol use. Formoterol was detected up to 8 h after administration in all volunteers with concentrations up to 19.6 ng.mL(-1) . From 28 routine samples, 27 had less than 10 ng.mL(-1) of formoterol and only in one of the samples the concentration was 25 ng.mL(-1) . Therefore, administration of formoterol by inhalation at the maximum dose allowed by WADA will not produce false positive results using a threshold concentration of 30 ng.mL(-1) , and the experience up to now in routine doping tests indicates that the probability of obtaining urines with concentrations greater than 30 ng.mL(-1) is close to nil. For this reason, sports authorities should re-evaluate the need of a threshold concentration for formoterol and its practical usefulness. Copyright © 2013 John Wiley & Sons, Ltd.Drug Testing and Analysis 04/2013; 5(4). DOI:10.1002/dta.1450 · 2.51 Impact Factor