Rosberg_1993_Eur.J.Clin.Pharmacol_45_147

Concentrations in cerebrospinal fluid (CSF) and plasma of bambuterol and its active metabolite, the beta 2-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 beta 2-adrenoceptor agonists to interact with central receptors.