!

COVID-19 Response

Access our COVID-19 Response homepage, with more information and resources during the COVID-19 pandemic, including what to do if you’re experiencing symptoms.

Jin Wang Lab

Teaching

Master
Heading

Suggested Reading

Content

Basic introduction to pharmacokinetics: credit to ASHP.org
Introduction to PK and PD
Basic PK

Excellent reading material for pharmacokinetics
Credit to Dr. Adam M. Persky at UNC-Chapel Hill
Foundations in Pharmacokinetics

History of Pharmacokinetics

Pharmacology Blog

Excel demo calculations for infusion, loading dose and multi dose

Derivation of drug plasma concentration as a function of time for infusion

The most commonly used PK analysis
Non-Compartmental Analysis (NCA)

Heading

Useful Tools

Content

Tenua
Free kinetics simulator. It can be used for chemical/enzymatic reactions and pharmacokinetics etc.

PK Solver
Free PK analysis Excel Add-on (PK analysis). Instructions to add PK Solver to Microsoft Excel 2016. Manual for PK Solver. Original Publication for PK Solver.

DrugBank
Comprehensive database for FDA-approved and experimental drugs

Heading

Volume of Distribution

Heading

Several Scenarios for Volume of Distribution

Content

Plasma Compartment:
If a drug has a very large molecular weight or binds extensively to plasma proteins, it is too large to move out through the endothelial slit junctions of the capillaries and, thus, is effectively trapped within the plasma (vascular) compartment. As a consequence, the drug distributes in a volume (the plasma) that is about 3 L of body fluid in a 75-kg individual. Heparin shows this type of distribution.
If a drug has a Vd of 3 L, drug is mostly in the plasma.
Explanation: Plasma water is approximately 3 L.

Extracellular Fluid:
If a drug has a low molecular weight but is hydrophilic, it can move through the endothelial slit junctions of the capillaries into the interstitial fluid. However, hydrophilic drugs cannot move across the lipid membranes of cells to enter the water phase inside the cell. Therefore, these drugs distribute into a volume that is the sum of the plasma water and the interstitial fluid, which together constitute the extracellular fluid. This is about twenty percent of the body weight, or about 18 L in a 75-kg individual. Aminoglycoside antibiotics show this type of distribution.

Total Body Water:
If a drug has a low molecular weight and is hydrophobic, not only can it move into the interstitium through the slit junctions, but it can also move through the cell membranes into the intracellular fluid. The drug, therefore, distributes into a volume of about sixty percent of body weight, or about 40 L in a 75-kg individual. Ethanol exhibits this apparent volume of distribution.
If a drug has Vd of ~40 L, drug is evenly distributed throughout the body.
Explanation: Total body water is approximately 40 L.

Other Sites:
In pregnancy, the fetus may take up drugs and thus increase the volume of distribution. Drugs that are extremely lipid-soluble, such as thiopental , may also have unusually high volumes of distribution.
If tissue binding exceeds plasma protein binding, Vd will be large (> 40L).
Explanation: Volume of distribution indicates whether drug resides primarily in the plasma or outside the plasma. Large volumes mean that drug has partitioned into tissue and thus, is outside of the plasma space.

If a drug is unable to cross membranes, Vd cannot be larger than the extracellular space.
Explanation: Again volume of distribution tells you where drug resides, in plasma or outside of plasma. If a drug cannot pass through membranes, it will remain outside of cells.

If plasma binding is stronger than tissue binding, Vd will be smaller than 40 L.
Explanation: Once again, volume of distribution indicates where the drug primarily resides, in plasma or outside of plasma. Small volumes mean that drug is sequestered in the blood and has not penetrated into tissue space.

Credit to this Pharmacology Blog