A new aminoglycoside antibiotic is developed that is believed to be particularly effective against Pseudomonas. The volume of distribution of the drug is measured in a group of volunteers and is determined to be 4.5 L. This new drug is most likely to have which of the following properties?

Question

A new aminoglycoside antibiotic is developed that is believed to be particularly effective against Pseudomonas.  The volume of distribution of the drug is measured in a group of volunteers and is determined to be 4.5 L.  This new drug is most likely to have which of the following properties?

Quizplus · Accepted Answer

The volume of distribution (V_d) refers to a hypothetical volume of fluid into which the administered amount of drug would need to be uniformly distributed to produce the observed plasma concentration. The volume of distribution is determined by administering a given amount of drug by the intravenous route and subsequently measuring the initial plasma concentration of the drug. The formula is as follows: V_d (L) = amount of drug given (mg) / plasma concentration of drug (mg/L) The average total body water is approximately 41 liters. Of that, the extracellular fluid volume is about 14 L, or 1/3 of total body water. Within the extracellular fluid, the plasma volume is about 3 L, and interstitial fluid makes up the rest. Initially, the drug enters the plasma compartment by the IV route. If a drug has a large molecular weight, is bound extensively to plasma proteins, or is highly charged (hydrophilic), then the drug generally remains in the plasma compartment and the volume of distribution is usually low as in the case above (about 3-5 liters). If the drug has a small molecular weight but is hydrophilic, it can distribute into the interstitial fluid compartment outside of the blood vessels as well as in the intravascular compartment. In these cases the volume of distribution is limited to a total volume of about 14-16 liters (plasma volume plus interstitial volume). If the drug has a small molecular weight and is also uncharged (hydrophobic or lipophilic), then the drug can cross cell membranes and reach intracellular compartment. These drugs have the highest volume of distribution (41 liters). Drugs that are avidly bound in the tissues exhibit the highest volumes of distribution, often much higher than the total body water volume, because these drugs accumulate readily within cells thereby maintaining low plasma concentrations. (Choice A) If the molecular weight of the drug is low, then the drug will tend to easily pass through endothelial junctions into the interstitial fluid, making the volume of distribution at least 14 liters. The Vd may be higher if the drug is also hydrophobic. (Choice B) Lipophilic drugs tend to readily cross cell membranes and distribute widely outside the plasma and interstitial compartments. This tendency to collect within cells gives these drugs a high volume of distribution. (Choice C) A drug with a V_d of 4.5 L, which is approximately the same as the plasma volume, is likely to be highly bound to plasma proteins such as albumin. Binding to plasma proteins tends to retain drug in the plasma compartment and prevent the diffusion of drug into the extravascular compartments. If this drug were not bound to albumin, it would be more likely to diffuse into the interstitium and a higher V_d would be expected. (Choice E) Bioavailability is a measure of absorption and is unrelated to the distribution of a drug. Educational Objective: Characteristics of a drug such as high molecular weight, high plasma protein binding, high charge, and hydrophilicity tend to trap the drug in the plasma compartment resulting in a low V_d (3-5 L).

A New Aminoglycoside Antibiotic Is Developed That Is Believed to Be