BAMBUTEROL AND TERBUTALINE IN HUMAN CEREBROSPINAL-FLUID AND PLASMA

Concentrations in cerebrospinal fluid (CSF) and plasma of bambuterol a nd its active metabolite, the beta2-adrenoceptor agonist terbutaline, were measured in man after four once-daily doses of 30 mg bambuterol h ydrochloride (Bambec(R)). Nine patients scheduled for orthopaedic surg ery under spinal anaesthesia completed the study. The concentrations o f 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 apparen t steady state. While the rank order of the ratios was expected from t he fractions of unbound bambuterol and terbutaline in plasma, their ab solute values were only about 1/6 (bambuterol) and 1/4 (terbutaline) o f those predicted from diffusion equilibria between plasma and CSF. Th us, the rates of transport of bambuterol and terbutaline from plasma i nto 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 agree ment with animal experiments and suggest that bambuterol and terbutali ne are less likely than lipophilic beta2-adrenoceptor agonists to inte ract with central receptors.