Dose proportionality of nadolol pharmacokinetics after intravenous administration to healthy subjects.

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Morrison RA, Singhvi SM, Creasey WA, Willard DA

Dose proportionality of nadolol pharmacokinetics after intravenous administration to healthy subjects.

Eur J Clin Pharmacol. 1988;33(6):625-8.

PubMed ID
3366166 [ View in PubMed
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Abstract

To support the increasing use of intravenous beta-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.

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