Pharmacokinetics and extrapulmonary b2 adrenoceptor activity of nebulised racemic salbutamol and its R and S isomers in healthy volunteers

with R-salbutamol already being cleared and S-salbutamol reaching peak levels at Background – Racemic salbutamol re30 minutes after the last dose (at t110). mains one of the most commonly used There were higher plasma levels of R-salbronchodilators in the treatment of rebutamol and S-salbutamol following adversible airways obstruction. Data from ministration of the respective isomers animal and human studies suggest that the alone compared with their levels after adS-isomer, whilst contributing no bronchoministration of the racemate, suggesting dilator activity, may induce increased an influence of each isomer on the clearbronchial hyperreactivity and may explain ance of the opposite isomer when given as the adverse effects of regular racemic sala racemate. butamol on asthmatic disease control. The Conclusions – The S-isomer of salbutamol purpose of this study was to evaluate the has no detectable activity at extradose-response effects of racemic (+/-) salpulmonary b2 adrenoceptors whilst exbutamol and its R(-) and S(+) isomers in hibiting higher plasma levels than the Rterms of pharmacokinetics and pharisomer, in keeping with greater clearance macodynamics at extrapulmonary b2 adof R-salbutamol than S-salbutamol. renoceptors when given by the inhaled Inhalation of R-salbutamol and RS-salroute to healthy volunteers. butamol produced dose-related b2 reMethods – Twelve healthy volunteers of sponses which were equivalent when mean age 20.6 years were studied in a compared on a 1:2 microgram basis, dedouble blind, placebo controlled, crossspite higher plasma levels of R-salbutamol over design comparing cumulative doubafter administration of the R isomer than ling doses of nebulised R-salbutamol (R) after administration of the racemate. Furand S-salbutamol (S) isomers (200 lg/ ther dose ranging studies are required at 400 lg/800 lg/1600 lg/3200 lg) and racemic steady state to evaluate the pharsalbutamol (RS) (400 lg/800 lg/1600 lg/ macokinetics of Rand S-salbutamol and 3200 lg/6400 lg). Doses were administered their relative effects on bronchial hyperat 20 minute intervals (t0/t20/t40/t60/t80) and reactivity when given on a regular basis to measurements were made of extraasthmatic subjects. pulmonary b2 responses as an increase in (Thorax 1997;52:849–852) finger tremor and heart rate and fall in plasma potassium at baseline and each