Beta-2-adrenoceptor-mediated hypokalemia and its abolishment by oxprenolol.
The time course and concentration-effect relationship of terbutaline-induced hypokalemia was studied, using computer-aided pharmacokinetic-dynamic modeling. Subsequently we investigated the efficacy of oxprenolol in antagonizing such hypokalemia, together with the pharmacokinetic interaction between both drugs. Six healthy subjects were given a 0.5 mg subcutaneous dose of terbutaline on two occasions: 1 hour after oral administration of a placebo and 1 hour after 80 mg oxprenolol orally. In the 7-hour period after terbutaline administration, plasma samples were taken for determination of plasma potassium levels and drug concentrations. The sigmoid Emax model offered a good description of the relation between terbutaline concentrations and potassium effects. Oxprenolol caused decreases of 65% and 56% of terbutaline volume of distribution and clearance, respectively, and an increase of 130% of its AUC. In spite of higher terbutaline concentrations after oxprenolol pretreatment, the hypokalemia was almost completely antagonized by the beta 2-blocking action.
Jonkers
R
R
Department of Medicine, Pharmacology, Academic Medical Center, Amsterdam, The Netherlands.
Van Boxtel
C J
CJ
Oosterhuis
B
B
D000328:Adult; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced* / Q000517:prevention & control; D010096:Oxprenolol / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013726:Terbutaline / Q000493:pharmacokinetics / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D010096:Oxprenolol; D013726:Terbutaline; D011188:Potassium