Uptake and displacement of [3H]-propranolol and [3H]-chlorpromazine in isolated, recirculating perfused guinea-pig lungs.
The pulmonary uptake of tritium labelled propranolol and chlorpromazine and their displacement by amphiphilic drugs has been studied in isolated guinea-pig lungs. Lungs were perfused by recirculation with 60 ml tyrode solution (carbogen gassed, 37 degrees C, 6% hydroxy-ethyl-starch) at a flow rate of 10 ml/min. In uptake experiments, a steady state was reached within 20 min with 95% of 10(-9) M propranolol and 90% of 10(-9) M chlorpromazine removed from the perfusate. Using 10(-4) M propranolol, a saturation process became evident, whereas no concentration dependency was observed for chlorpromazine uptake. Kinetic analysis revealed similar uptake rates, but different capacities for both compounds. In displacement experiments, 10(-9) M propranolol was displaced by 10(-4) M amphiphilic drugs in the order: chlorpromazine greater than propranolol greater than alprenolol greater than tetracaine. No displacement occurred by practolol, indomethacin or phenylbutazone. The results indicate that the lungs have a large binding capacity for amphiphilic drugs. These compounds can interfere with each other, according to their lipophilicity, their steric configuration and charges.
Heinzow
B
B
Department of Pharmacology, Christian-Albrechts University, Kiel, F.R.G.
Lüllmann
H
H
Staib
L
L
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D002746:Chlorpromazine / Q000378:metabolism* / Q000493:pharmacokinetics; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000378:metabolism* / Q000493:pharmacokinetics; D013997:Time Factors
D011433:Propranolol; D002746:Chlorpromazine