Pharmacokinetics of Inhaled Monodisperse Fluticasone Propionate

The clinical trial is to investigate the pharmacokinetic effects (that is how much drug is in the blood) of Fluticasone Propionate (Flixotide), a commonly used steroid drug that is inhaled in patients with asthma. We will use standard clinical Flixotide Nebules that are used with clinical nebulisers (machines used in hospital and at home - to deliver drug to patients with asthma). Current clinical nebulisers deliver a 'coarse' mist of drug, which has the potential for side effects and this is an important consideration with steroids. These Flixotide nebules will be used to deliver the drug (fluticasone propionate) as monodisperse aerosol clouds (that is the drug will be delivered as a 'fine' mist cloud to patients). In order to deliver the drug as a monodisperse aerosol, the Flixotide Nebules will be used with a spinning top aerosol (a large research nebuliser machine)which is able to selectively generate aerosol clouds that have a fine mist. A fine mist cloud leads to less deposition in the throat of the patients and a greater control of the inhaled drug reaching the lungs, and fine mist drug clouds have the potential to reduce side effects. We will also compare this to the use of a standard routine clinical dose of a Flixotide metered-dose inhaler ( a 'press and breathe' inhaler) with a spacer (plastic bubble on the end of an inhaler) delivered to patients.

Inclusion criteria

Healthy Volunteers

Participants will be included if they meet all of the following inclusion criteria

• Healthy non smoking participants
• Male or female aged above 18 years
• No history of respiratory disease
• Normal baseline spirometry as predicted for age, sex and height (we have excluded those with abnormal spirometry as this may indicate an underlying lung condition that needs attention, and such participants will be told their result and with their consent, the information will be forwarded to their General Practitioner, as part of the safety and well being of the research participant.
• No history of allergic disease i.e., a negative skin prick test
• Participants who are free from significant cardiac, gastrointestinal, hepatic, renal, hematological, neurological and psychiatric disease.
• Not taking any regular medication that is contraindicated in those about to receive fluticasone propionate (as indicated in the British National Formularly); other than the oral contraceptive pill.

Asthmatics

• Male or females aged greater than 18 years with a documented history of reversible airways disease responding to beta2-adrenergic therapy.
• Asthmatic patients who are free from significant cardiac, gastrointestinal, hepatic, renal, hematological, neurological and psychiatric disease.
• Patients who are stabilized on 500 micrograms or less of inhaled beclomethasone dipropionate or alternative inhaled corticosteroid (budesonide or ciclesonide).
• Patients who are able and willing to give written informed consent to take part in the study
• Not taking any regular medication that is contraindicated in those about to receive fluitcasone propionate (as indicated in the British National Formularly); other than the oral contraceptive pill.

Exclusion criteria

Healthy Volunteers and Asthmatics

• Those requiring maintenance oral or parenteral corticosteroid therapy for their airways disease or patients who have ceased maintenance oral or parenteral corticosteroid therapy within the four weeks prior to visit 1
• Those requiring greater than 500 micrograms of inhaled beclomethasone dipropionate or alternative inhaled corticosteroid (budesonide or ciclesonide).
• Subjects that have received inhaled or intravenous fluticasone propionate in the last 2 months.
• Those whose reversible airways obstruction has been unstable in the last four weeks (indicated by any change in their maintenance therapy).
• Those participants who have had a lower respiratory tract infection in the previous four weeks
• Those who have donated 450ml blood or more within the previous 1 month.
• Those who have a history of drug allergy which, in the opinion of the Unit Physician, contraindicates his/her participation in the study.
• Any evidence of a positive pregnancy urine test for female volunteers or females who are pregnant or lactating or are likely to become pregnant during the trial. Women of child-bearing potential may be included in the study if, in the opinion of the investigator, they are taking adequate contraceptive precautions.
• Participants with a known or suspected allergy to corticosteroids or any component of the formulations and/or Suspected hypersensitivity to inhaled corticosteroid (this will be asked directly at the screening visit).
• Any patient with a contraindication to taking an inhaled steroid and specifically FP, listed in the British National Formularly will not be entered into this study
• Those who have experienced an acute asthma exacerbation requiring emergency room treatment and/or hospitalization within one month of visit 1.