Dose proportionality of nadolol pharmacokinetics after intravenous administration to healthy subjects
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To support the increasing use of intravenous β-blockers during cardiovascular emergency and surgery, dose proportionality of pharmacokinetics of nadolol was evaluated after intravenous administration of 14C-nadolol at doses of 1, 2 and 4 mg to nine healthy volunteers. There were no observed differences in the excretion or the pharmacokinetics of nadolol with respect to the dose administered. Over a 72-h period after drug administration, an average of about 60% of the dose was excreted in the urine and about 15% was excreted in the feces. The range of values for total body clearance (219 to 250 ml·min−1), renal clearance (131 to 150 ml·min−1), mean residence time (10.5 to 11.3 h), half-life (8.8 to 9.4 h), and steady-state volume of distribution (Vss) (147 to 157 l) indicated that nadolol was extensively distributed and slowly cleared from the body. There was a linear correlation (r2=0.97) between the area under the plasma concentration of nadolol versus time curve (AUC) and the dose. All pharmacokinetics parameters, except Vss, were slightly, but significantly, different at the 4 mg dose. Superposition of the dose-normalized average concentrations indicated that despite these minor differences in parameters, the pharmacokinetic behavior of nadolol was linear with respect to dose. Urinary excretion of nadolol was dose independent.
Key wordsnadolol pharmacokinetics 14C-nadolol healthy volunteers i.v. administration
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