Racial differences in drug response: isoproterenol effects on heart rate following intravenous metoprolol.
Healthy young black men and white men received single intravenous doses of metoprolol (0.07 mg/kg) or participated in an isoproterenol sensitivity study before and after metoprolol (0.07 mg/kg followed by 50 micrograms/min) in a randomized, crossed-over fashion. Noncompartmental pharmacokinetic parameters were calculated. The dose of isoproterenol versus change in heart rate response curves were constructed, and comparisons of dose ratio, ED50, Emax, and Ka, with the apparent association constant for metoprolol binding to beta 1-receptors, were made. There were no pharmacokinetic differences observed between the groups. The predicted Emax for the black group was 52.7 +/- 8.7 beats/min at a metoprolol concentration of 29.8 +/- 6.1 ng/ml, which was higher (p less than 0.05) than that in the white group, i.e., 43.7 +/- 7.3 beats/min at a concentration of 27.6 +/- 9.1 ng/ml. There were no differences in dose ratio, ED50, or Ka. The racial differences in beta 1-receptor responses to exogenous isoproterenol following metoprolol can simply be explained by an increase in beta 1-receptor activity in the black subjects, assuming homogeneity in cardiac beta 2-receptor responses.
Rutledge
D R
DR
Department of Pharmacy Practice, College of Pharmacy, Wayne State University, Detroit, MI 48202.
Steinberg
J
J
Cardozo
L
L
D000328:Adult; D004336:Drug Antagonism; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate; D008790:Metoprolol / Q000493:pharmacokinetics*; D044469:Racial Groups; D011897:Random Allocation; D013223:Statistics as Topic
D008790:Metoprolol; D007545:Isoproterenol