Abstract
The novel method of estimating the volume of distribution involves (a) administering an appropriate bolus intravenous dose of the drug, (b) starting a constant-rate intravenous infusion of the drug at the same time, (c) maintaining the infusion for a given number of hours, (a) measuring the drug concentration over the entire time course, (e) computer-fitting the post-infusion data to obtain estimates of Vm and Km, (f) estimating the total area under the concentration-time curve from zero time to infinity, and (g) iteratively solving a cubic equation to obtain the estimate of the volume of distribution. The method was applied to ethanol in the cat and yielded an average value of 635ml/kg (63.5% of body weight) with a coefficient of variation of 23.0%. This is equivalent to total body water in the cat.
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Work performed in the Upjohn Center for Clinical Pharmacology, The Univeristy of Michigan Medical School, Ann Arbor, Michigan 48109.
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Lin, YJ., Weidler, D.J., Garg, D.C. et al. Novel method of estimating volume of distribution of a drug obeying Michaelis-Menten elimination kinetics. Journal of Pharmacokinetics and Biopharmaceutics 6, 197–207 (1978). https://doi.org/10.1007/BF01312262
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DOI: https://doi.org/10.1007/BF01312262