Drug distribution volume

The levels of circulating drug that are achieved are a function of dose, absorption efficiency, overall bioavailability, distribution, and also clearance. The major determinant of drug distribution volume is its lipo-philicity. As lipophilicity increases, so does the ability of the drug to cross biological membranes and move into extravascular environments, particularly into fatty tissue and the central nervous system (CNS). 

Klotz, U. (1976) Pathophysiological and disease-induced changes in drug distribution volume pharmacokinetic implications. Clinical Pharmacokinetics, 1, 204-218. 

With respect to the definition of the term in the denominator represents in fact that part of the drug-distribution volume which is totally cleared from the drug per unit of time. It is easy to recognize that such a relationship offers an opportunity of estimating the total (plasmatic) clearance. The estimation may be made according to the formula ... 

Because disturbances in fluid balance are routinely encountered in clinical medicine, it is essential to have a thorough understanding of body fluid compartments and the therapeutic use of fluids. Similarly, disturbances in serum sodium, potassium, calcium, phosphorus, and magnesium are ubiquitous and must be mastered by all clinicians. Dysregulation of fluid and/or electrolyte status has serious implications regarding the concepts of drug absorption, volumes of distribution, and toxicity. Similarly, many medications can disrupt fluid and/or electrolyte balance as an unintended consequence. 

Drug therapy individualization for patients with renal insufficiency sometimes requires only a simple proportional dose adjustment based on creatinine clearance (CLcr). Alternatively, complex adjustments are required for drugs that are extensively metabolized or undergo dramatic changes in protein binding and distribution volume. 

Unchanged passive diffusion and no change in bioavailability for most drugs l Active transport and i bioavailability for some drugs l First-pass extraction and T bioavailability for some drugs i Volume of distribution and T plasma concentration of water-soluble drugs T Volume of distribution and T terminal disposition half-life (t ) for fat-soluble drugs... 

The theoretical volume into which a drug distributes following its administration (ml)... 

The relationship between the amount of drug and its concentration is classically represented by the following equation, which functions as if there were a physical space (called distribution volume) throughout, which the drug distributes evenly ... 

The plasma concentration at when divided by the dose gives an estimate of distribution volume that can be used to calculate dosing for fast equilibrating drug, in particular, such as anesthetics. This distribution volume term often proves more useful than the traditional central volume of distribution or the steady-state distribution volume. 

The three main parameters of clinical pharmacokinetics are clearance, distribution volume, and bioavailability. Clearance is the rate at which the body eliminates a drug. In order to achieve a steady-state concentration, the drug must be given so that the rate of clearance equals the rate of administration. If the drug is given as quickly as it is eliminated, a consistent level in the body will be maintained. 

Distribution - Valproic acid is rapidly distributed. Volume of distribution of total or free valproic acid is 11 or 92 L/1.73 m, respectively. Valproic acid has been detected in CSF (approximately 10% of total concentrations) and milk (about 1% to 10% of serum concentrations). Therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate. The plasma protein binding of valproate is concentration-dependent. Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairment, and in the presence of other drugs (eg, aspirin). Conversely, valproate may displace certain protein-bound drugs (eg, phenytoin, carbamazepine, warfarin, tolbutamide). 

By itself, volume of distribution does not provide any insight into mechanisms of drug distribution, however it is a useful descriptive index of how well the drug... 

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