Drug plasma binding

Because it is generally assumed that only unbound drug is available for uptake across cell membranes and therefore determines distribution and possibly elimination of a drug, it is likely that changes in drug plasma binding (secondary to alterations in plasma lipoprotein binding) will affect pharmacokinetic parameters such as volume of distribution (VD) and clearance (CL). 

The inhalation route for administering drugs into the pulmonary system for treatment of respiratory diseases eliminates many bioavailability problems such as plasma binding and first-pass metabolism, which are encountered in parenteral or oral administration. Consequently, a small inhalation dose is adequate for achieving... 

Drug-protein binding is the reversible interaction of drugs v/ith different proteins in plasma. Albumin is not the exclusive protein involved. Drugs bind to specific sites on the protein. 

Following its uptake into the body, the drug is distributed in the blood (1) and through it to the various tissues of the body. Distribution may be restricted to the extracellular space (plasma volume plus interstitial space) (2) or may also extend into the intracellular space (3). Certain drugs may bind strongly to tissue structures, so that plasma concentrations fall significantly even before elimination has begun (4). 

Competition between drugs for plasma binding sites occurs and is responsible for some of the clinically most important changes in drug distribution. Phenylbutazone and oxyphenbutazone, for example, potentiate the action of warfarin by displacement (A2) and trichloroacetic acid, a major metabolite of chloral hydrate has a similar effect (S12) and is the cause of hemorrhagic complications during coumarin therapy (A2). 

Y Ishihama, T Miwa, N Asakawa. Drug-plasma protein binding assay by electrokinetic chromatography-frontal analysis. Electrophoresis 23 951-955... 

A Shibukawa. Development of high-performance frontal analysis and application to drug-plasma protein binding study. Yakugaku Zasshi 118 554-565, 1998 (in Japanese). 

Musteata, F.M., Pawliszyn, J., Qian, M.G., Wu, J.-T. and Miwa, G.T. (2006) Determination of drug plasma protein binding by solid phase microextraction. Journal of Pharmaceutical Sciences, 95, 1712-1722. 

Phenprocoumon has a long plasma half-life of 5 days and thus a duration of action that can last 7-10 days. On the other hand acenocoumarol has a half-life of 10-24 hours and therefore a shorter duration of action. The half-life of warfarin ranges from 25-60 hours and its the duration of action is 2-5 days. Both warfarin and phenprocoumon are highly protein bound and interactions may occur with other drugs that bind to albumin. 

Pharmacokinetics Rapidly and extensively absorbed after PO administration (food decreases drug plasma concentration but doesn t affect absorption). Protein binding 97%, Completely hydrolyzed to active metabolite mycophenolic acid. Primarily excreted in urine. Not removed by hemodialysis. Half-life 17,9 hr. 

For drugs that bind to serum proteins, equilibrium exists between the bound or ineffective portion and the unbound (free) or effective portion. For acidic drugs that are highly bound to albumin, the free plasma concentration may correlate best with pharmacologic effect. Although albumin levels decrease only slightly with age, they tend to decrease during periods of illness. This can result in elevated levels of... 

Tissue binding versus plasma binding of drugs General principles and pharmacokinetic consequences, 20, 117... 

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