Studies of Renal Excretion of Creatinine. II. Volume of Distribution

Abstract

A discussion of the antagonism existing between insulin and adrenalin will not be given in this preliminary report. Adrenaliii dilutions were made only at the beginning of an experiment and it is not known how much cleterioration occurred. However, the rate of injection at the beginning of the experiment was within the range of epinephrine secretion found liy Stewart and Rogoff in blood coming from the adrenal glands (0.00015-0.001 mg. per kilo per minute). More experiments are being conducted, but our results so far seem to indicate that the hypophysectomized animals require more adrenalin to prevent convulsions following insulin than animals subjected to suppression of epinephrine secretion from the adrenals. Further, it woulcl seem probable that the hypophysectomized animal does not liberate effective amounts of adrenalin during insulin hypoglycemia. C Studies of Renal Excretion of Creatinine.By studying the time change of the concentration of a substance in the plasma and of its simultaneous rate of excretion in the urine, the conclusion has been reached'' that both these quantities decrease exponentially to the pre-ingestion level and furthermore, that the coefficients of the time in both exponential functions are equal, on an average, for a given substance. From these 2 facts it follows that the rate of excretion of a substance obeying such laws is proportional to the plasma concentration at any time. The abo,ve statements have been verified so far only for creatinine and xylose.In symbols we have 2Stewart and Rogoff, Am.

Quantitative Structure – Pharmacokinetics Relationships Analysis of Basic Drugs: Volume of Distribution

“…It has been defined as a hypothetical volume of body fluid that would be required to dissolve the total amount of drug at the same concentration as that found in plasma (3). Three types of volume of distribution are classically reported in the literature: VD of the central compartment (VD c ), VD during the terminal phase (VD  or VD area ) and VD at steady state (VD ss ).…”

The Connection Between the Steady State (Vss) and Terminal (Vβ) Volumes of Distribution in Linear Pharmacokinetics and The General Proof That Vβ ≥ Vss

“…The concept of volume of distribution was originally introduced by Dominguez 1 and defined as the hypothetical ''volumes of body fluids dissolving the substance at the same concentration as plasma.'' The commonly used noncompartmental equations for the estimation of the steady state and terminal volumes of distribution (as well as the mean residence time) are sometimes presented and used as the definitions of these parameters, which obscures their meaning.…”

History of pharmacokinetics

“…During the period 1939 to 1950, Dominquez in the United States made significant contributions with articles on the pharmacokinetics of creatinine, mannitol, xylose and galactose (Dominguez, 1934;Dominguez and Pomerene, 1934;Dominguez et al, 1935;Pomerene, 1944, 1945a,b;Dominguez et al, 1947a and1947b;Dominguez, 1950). He introduced the concept of the volume of distribution and defined it as the hypothetical volume of body fluid dissolving the substance at the same concentration as that in plasma (Dominguez, 1934). Dominguez was also the first to derive and apply Eqn (3) to estimate the rate of absorption of a substance as a function of time.…”