Effect of salbutamol on digoxin pharmacokinetics.
A single dose of the beta 2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a beta 2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 micrograms.kg-1.h-1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i.v. injection of digoxin 15 micrograms.kg-1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0-6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium.(ABSTRACT TRUNCATED AT 250 WORDS)
Edner
M
M
Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
Jogestrand
T
T
Dahlqvist
R
R
D000328:Adult; D000420:Albuterol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009132:Muscles / Q000378:metabolism*; D011188:Potassium / Q000097:blood
D004077:Digoxin; D000420:Albuterol; D011188:Potassium