Pharmacokinetics: Distribution

Distribution is the process of a substance leaving the blood stream and moving to cells or tissues.

Absorptive phase

After a drug is absorbed (or injected) into the blood stream, it may be distributed into interstitial and cellular fluids, then into various tissues. In the blood, the drug may be “free” or bound to plasma proteins. Only the free drug is further distributed. An initial phase of distribution may be distinguished that reflects cardiac output and regional blood flow.

a. Heart, liver, kidney, brain, & other highly perfused organs receive most of drug in initial phase of distribution.

b. A second phase involves delivery of the drug to muscle, viscera, skin, and fat (minutes to hours before equilibration). This is limited by blood flow but involves far larger fraction of body mass.

Distribution is also limited by drug binding to plasma proteins (p. 35) Drawing of blood for drug “blood levels” measures both bound and free drug in the blood but does not include drug bound in tissues or at receptor sites.

The concentration gradient across the plasma membrane for the diffusible fraction (lipid soluble, nonionized, unbound) determines both rate and direction of net transfer between plasma and tissues. The blood supply to the tissue may also affect the concentration gradient (poor tissue perfusion fails to carry the drug away from the absorption site).

A hypothetical quantitative estimation of drug distribution is called the volume of distribution (Vd). This provides some estimate of how much drug has entered the body and where it went (e.g., extracellular fluids; muscle; fat tissue).

Category: Pharmacology Notes