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Objectives: To compare the relative systemic dose potency and tolerability of inhaled formoterol and salbutamol and to describe elimination of formoterol, particularly any enantioselectivity. Methods: Twelve healthy subjects, aged 18–28 years, completed three open study days, and eleven asthmatic patients, aged 20–56 years, completed four double-blind study days in randomised, placebo-controlled and crossover fashions. The healthy subjects inhaled 13.5 + 13.5 + 27 μg formoterol (Oxis) via Turbuhaler and 300 + 300 + 600 μg salbutamol (Ventoline) via a pressurised metered dose inhaler (pMDI). The asthmatics, being on formoterol 9 μg twice daily via Turbuhaler during the study, inhaled the same single doses as the healthy subjects plus 900 + 900 + 1800 μg salbutamol via pMDI. Doses were given cumulatively 30 min apart on separate study days. Placebo was a day of no treatment in the healthy subjects. Double dummies were used for the asthmatics. Cardiovascular and metabolic effects were evaluated. Elimination of formoterol was addressed in the healthy subjects. Results: Formoterol was estimated to be 28–109 times as potent as salbutamol, depending on the systemic effect variable. The duration of systemic action seemed to differ marginally at approximately equieffective doses of formoterol and salbutamol. Systemic effects were well tolerated and tended to be more pronounced in the healthy subjects than in the asthmatic patients. The half-life of the pharmacologically more active (R;R)-formoterol was longer than that of (S;S)-formoterol. Conclusions: Systemically, formoterol was shown to be 28–109 times as potent as salbutamol. Equieffective doses seemed to have a similar duration of effect. Formoterol and salbutamol were well tolerated by healthy subjects up to the tested total doses of 54 μg and 1200 μg, respectively, and by asthmatic patients up to the tested total doses of 54 μg and 3600 μg, respectively. Elimination of formoterol was enantioselective. [ABSTRACT FROM AUTHOR]

Concentrations in cerebrospinal fluid (CSF) and plasma of bambuterol and its active metabolite, the β-adrenoceptor agonist terbutaline, were measured in man after four once-daily doses of 30 mg bambuterol hydrochloride (Bambec). Nine patients scheduled for orthopaedic surgery under spinal anaesthesia completed the study. The concentrations of both substances were much lower in CSF than in plasma, the ratio CSF/plasma being 0.09 for bambuterol and 0.19 for terbutaline, at apparent steady state. While the rank order of the ratios was expected from the fractions of unbound bambuterol and terbutaline in plasma, their absolute values were only about 1/6 (bambuterol) and 1/4 (terbutaline) of those predicted from diffusion equilibria between plasma and CSF. Thus, the rates of transport of bambuterol and terbutaline from plasma into the central nervous system appear to be slow relative to transport out of the system, e.g. by outflow of CSF. The findings are in agreement with animal experiments and suggest that bambuterol and terbutaline are less likely than lipophilic β-adrenoceptor agonists to interact with central receptors. [ABSTRACT FROM AUTHOR]