Abstract
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
Original language | English |
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Pages (from-to) | 627-633 |
Journal | Clinical Pharmacology and Therapeutics |
Volume | 42 |
Issue number | 6 |
Publication status | Published - 1987 |