Bambuterol: uptake and metabolism in guinea pig isolated lungs.
The lung uptake and biotransformation of 3H-bambuterol, a prodrug to terbutaline, were studied using isolated perfused and ventilated guinea pig lungs. 14C-Sucrose was used as an extracellular marker. The lung uptake of bambuterol was significantly (0.05 greater than or equal to P greater than or equal to 0.001) higher than that found for sucrose in single-pass perfusion experiments. High-performance liquid chromatographic (HPLC) analysis showed that 95.6 +/- 3.6% of the effluent 3H radioactivity was attributable to bambuterol. In recirculating experiments (120 min) the lung biotransformation of 3H-bambuterol (8.5 pmol/ml) was studied. Both oxidative and hydrolytic metabolism took place. The dominating metabolites were hydroxylated bambuterol and the monocarbamate derivative which is a product of hydrolysis of bambuterol. Traces of terbutaline were also formed. The results show that bambuterol has a certain affinity to lung tissue and that the drug is, to some extent, biotransformed in the guinea pig lung.
Ryrfeldt
A
A
AB Astra, Safety Assessment, Södertälje, Sweden.
Nilsson
E
E
Tunek
A
A
Svensson
L A
LA
D000818:Animals; D001711:Biotransformation; D001993:Bronchodilator Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D012588:Scintillation Counting; D013726:Terbutaline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
D001993:Bronchodilator Agents; D013726:Terbutaline; C047766:bambuterol