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Biomedical subjects

B J Lipworth

Publications and source records attributed to B J Lipworth.

At least 19 recordsLinked to original sources
PubMed2001

Dose-response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate.

AIMS: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA-beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). METHODS: Sixteen healthy volunteers were randomised in placebo-controlled single blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 microg day(-1), with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log-transformed to normalize their distribution. RESULTS: Urine and serum cortisol were suppressed by 2000 microg FP and BDP vs placebo and by 1000 microg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 microg BDP vs 1000 microg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol(-1) with BDP than FP at 1000 microg: n = 8/16 vs n = 2/16 (P < 0.05). CONCLUSIONS: There was dose-related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA-BDP than HFA-FP at 1000 microg. This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.

Administration, Inhalation↗
PubMed2001

Pharmacokinetics and systemic beta2-adrenoceptor-mediated responses to inhaled salbutamol.

AIMS: To examine whether systemic beta2-adrenoceptor responses, such as tachycardia, tremor and hypokalaemia, can be used as a surrogate for the 20 min pharmacokinetic profile of inhaled salbutamol. METHODS: A retrospective analysis of eight separate published studies in healthy volunteers was performed, each with an identical protocol evaluating the early lung absorption profile of a nominal 1200 microg dose of salbutamol given by different inhaler devices. Peak postural finger tremor, plasma potassium and heart rate were assessed. RESULTS: We found the maximum (Cmax) and average (Cav) plasma concentrations of salbutamol to be correlated (P < 0.0001) to change in plasma potassium (Cmax r = 0.904; Cav r = 0.899) and tremor (Cmax r = 0.875; Cav r = 0.857). No significant correlations existed between change in heart rate and Cmax (r = 0.425) or Cav (r = 0.415). CONCLUSIONS: Systemic beta2-adrenoceptor responses, in particular hypokalaemia and tremor, but not heart rate, appear to be good surrogates for evaluating the lung delivery of inhaled salbutamol. Consequently it is suggested that potassium or tremor responses may be used to evaluate the relative lung delivery of salbutamol from different inhaler devices.

Administration, Inhalation↗
PubMed2001

A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma.

BACKGROUND: Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy. OBJECTIVE: To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms. RESULTS: There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.

Acetates↗
PubMed2001

Comparative in vivo lung delivery of hydrofluoroalkane-salbutamol formulation via metered-dose inhaler alone, with plastic spacer, or with cardboard tube.

STUDY OBJECTIVE: To compare the lung delivery of chlorofluorocarbon-free salbutamol via a pressurized metered-dose inhaler (pMDI) alone, a pMDI with a small-volume plastic spacer, and a pMDI with a cardboard tube. DESIGN: A randomized, single (investigator)-blind, three-way, crossover study. SETTING: The Asthma and Allergy Research Group, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK. PARTICIPANTS: Twelve healthy volunteers aged 16 to 65 years. INTERVENTIONS: The subjects were administered 400 microg of salbutamol via a pMDI alone, via a pMDI plus a small-volume plastic spacer, or via a pMDI plus a cardboard tube. MEASUREMENTS AND RESULTS: Blood samples for plasma salbutamol concentrations were taken at 5 min, 10 min, and 20 min after inhalation, to measure lung bioavailability as a surrogate for relative lung dose. The addition of the plastic spacer resulted in a significantly higher maximal plasma salbutamol concentration (CMAX) and average plasma salbutamol concentration (CAV) than the pMDI used alone. This amounted to a 1.48-fold (32%) difference (95% confidence interval [CI], 1.03 to 2.13) for CMAX and a 1.42-fold (30%) difference (95% CI, 1.01 to 2.00) for CAV. There was no significant difference in the CMAX or CAV comparing the addition of the cardboard tube with the plastic spacer or the pMDI alone. CONCLUSIONS: Using a chlorofluorocarbon-free pMDI with a plastic spacer produced statistically, but not biologically, significant greater lung delivery of salbutamol. If a spacer is required for reasons other than increasing delivered drug dose, then the addition of a readily available cardboard tube will fulfill many of the required functions with no expense to the patient.

Administration, Inhalation↗
PubMed2001

Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids.

OBJECTIVE: To assess the addition of a leukotriene receptor antagonist and a long-acting beta(2)-agonist as second-line therapy in asthma. DESIGN: Placebo-controlled, double-dummy, crossover study. SETTING: Outpatient clinic. PATIENTS: Twenty patients with persistent asthma not controlled with inhaled corticosteroid therapy. INTERVENTIONS: Montelukast 10 mg once daily, or salmeterol, 50 microg bid, each for 2 weeks with 1-week run-in and washout placebo periods. MEASUREMENTS AND RESULTS: Adenosine monophosphate (AMP) bronchial challenge, blood eosinophil count (EOS), exhaled nitric oxide, and lung function after both placebo periods and after the first and last doses of each active treatment. Patients recorded their domiciliary peak expiratory flow (PEF), asthma symptoms, and rescue bronchodilator requirement (RES) twice daily throughout the study. For the primary end point of the provocative concentration of AMP causing a 20% fall in FEV(1), compared to placebo (47.5 +/- 13.0 mg/mL), there were significant differences with the first (114.1 +/- 36.9 mg/mL) and last (94.2 +/- 30.4 mg/mL) doses of montelukast as well as the first (160.1 +/- 64.5 mg/mL) but not the last (70.1 +/- 23.7 mg/mL) dose of salmeterol. Only montelukast produced significant suppression of the EOS. Neither drug affected exhaled nitric oxide levels. There were significant improvements with the first doses of salmeterol for all parameters of lung function. After 2 weeks of treatment, there were significant improvements with both drugs for RES and morning PEF. There were no significant differences between drugs for any end points except EOS. CONCLUSIONS: Montelukast and salmeterol exhibited significant improvements in asthma control when given as second-line therapy. Montelukast also produced significant effects on AMP challenge and EOS suggesting anti-inflammatory activity.

Acetates↗