Volume kinetics is a method used for analyzing and simulating the distribution and elimination of infusion fluids. Approximately 50 studies describe the disposition of 0.9% saline, acetated and lactated Ringer's solution, based on repeated measurements of the hemoglobin concentration and (sometimes) the urinary excretion. The slow distribution to the peripheral compartment results in a 50-75% larger plasma dilution during an infusion of crystalloid fluid than would be expected if distribution had been immediate. A drop in the arterial pressure during induction of anesthesia reduces the rate of distribution even further. The renal clearance of the infused fluid during surgery is only 10-20% when compared with that in conscious volunteers. Some of this temporary decrease can be attributed to the anesthesia and probably also to preoperative psychologic stress or dehydration. Crystalloid fluid might be allocated to "nonfunctional" fluid spaces in which it is unavailable for excretion. This amounts to approximately 20-25% during minor (thyroid) surgery.

Variability in the rate and extent of absorption, distribution and elimination of ethanol has important ramifications in clinical and legal medicine. The speed of absorption of ethanol from the gut depends on time of day, drinking pattern, dosage form, concentration of ethanol in the beverage, and particularly the fed or fasting state of the individual. During the absorption phase, a concentration gradient exists between the stomach, portal vein and the peripheral venous circulation. First-pass metabolism and bioavailability are difficult to assess because of dose-, time- and flow-dependent kinetics. Ethanol is transported by the bloodstream to all parts of the body. The rate of equilibration is governed by the ratio of blood flow to tissue mass. Arterial and venous concentrations differ as a function of time after drinking. Ethanol has low solubility in lipids and does not bind to plasma proteins, so volume of distribution is closely related to the amount of water in the body, contributing to sex- and age-related differences in disposition. The bulk of ethanol ingested (95-98%) is metabolised and the remainder is excreted in breath, urine and sweat. The rate-limiting step in oxidation is conversion of ethanol into acetaldehyde by cytosolic alcohol dehydrogenase (ADH), which has a low Michaelis-Menten constant (Km) of 0.05-0.1 g/L. Moreover, this enzyme displays polymorphism, which accounts for racial and ethnic variations in pharmacokinetics. When a moderate dose is ingested, zero-order elimination operates for a large part of the blood-concentration time course, since ADH quickly becomes saturated. Another ethanol-metabolising enzyme, cytochrome P450 2E1, has a higher Km (0.5-0.8 g/L) and is also inducible, so that the clearance of ethanol is increased in heavy drinkers. Study design influences variability in blood ethanol pharmacokinetics. Oral or intravenous administration, or fed or fasted state, might require different pharmacokinetic models. Recent work supports the need for multicompartment models to describe the disposition of ethanol instead of the traditional one-compartment model with zero-order elimination. Moreover, appropriate statistical analysis is needed to isolate between- and within-subject components of variation. Samples at low blood ethanol concentrations improve the estimation of parameters and reduce variability. Variability in ethanol pharmacokinetics stems from a combination of both genetic and environmental factors, and also from the nonlinear nature of ethanol disposition, experimental design, subject selection strategy and dose dependency. More work is needed to document variability in ethanol pharmacokinetics in real-world situations.

The dilution of the blood and the retention of infused Ringer's solution in the body increases in the presence of hypovolemia, which can be attributed chiefly to a reduction of the elimination rate constant.

The distribution of intravenous fluids can be analyzed by a kinetic model adapted for fluid spaces, but slightly different results are obtained, depending on the marker used to indicate dilution of the primary fluid space. Analysis and simulation of plasma volume expansion by this model is a tool that can help the anesthetist to better plan fluid therapy.

The relative efficiency of crystalloid infusion fluids differs depending on whether the entire dilution-time profile or only the maximum dilution is compared. Kinetic analysis and simulation is a useful tool for the study of such differences.