INVESTIGATION OF URINARY LEVELS OF SALBUTAMOL IN ASTHMATIC-PATIENTS RECEIVING INHALED THERAPY

Aim: Some studies have indicated that over-reliance on inhaled broncho dilator (beta(2)-agonist) therapy may worsen asthma control and increa se morbidity. The aim of this study was to measure urinary concentrati ons of salbutamol, the most commonly used bronchodilator, in a relativ ely large sample of asthmatic patients and examine the potential value of the concentration as an indicator of over-use of salbutamol. Metho d: The urinary concentrations of the drug were measured in 'spot' urin e samples from 102 asthmatic patients (64 community patients and 38 ho spital inpatients). A solid-phase extraction technique, using a phenyl -bonded phase and a reversed-phase ion-pair high-performance liquid ch romatography assay with UV-detection were developed and used to measur e both unchanged salbutamol concentrations and total salbutamol concen trations after enzymatic hydrolysis of the metabolite. In addition, sa lbutamol concentrations were corrected for urine dilution, with the me asured drug expressed per gram of urinary creatinine. Results: The hos pital patients were generally older, had greater disease severity, wer e more likely to be receiving prophylactic therapy and had received mo re salbutamol in the past 24 h. The urinary concentrations of salbutam ol varied enormously between patients. The median concentrations of un changed and total drug were 0.38 mu g/ml (range 0-34.4 mu g/ml) and 2. 55 mu g/ml (range 0-49.8 mu g/ml), respectively. Even when controlling for dosage in the preceding 24 h, there was a 262-fold and 810-fold v ariation in the urinary concentrations for unchanged and total salbuta mol, respectively, among the community patients. Modest correlations w ere found between salbutamol concentrations and dosage administered in the preceding 24 h (Spearman's r = 0.67 and 0.54 for unchanged and to tal drug, respectively; P < 0.001). The correlations improved only sli ghtly with correction for urine dilution (Spearman's r = 0.69 and 0.57 for unchanged and total drug, respectively; P < 0.001). Conclusion: T his enormous inter-patient variability, which may be largely due to di fferences in the pharmacokinetics of salbutamol and inhaler technique, may play a role in the observed worsening of asthma control with the regular use of inhaled bronchodilator drugs and warrants further inves tigation. Measuring urinary concentrations of salbutamol in spot sampl es provides only a relatively crude indication of the extent of use of inhaled salbutamol in the preceding 24 h.