What is considered a free drug in the bloodstream?

The term "free drug" in the bloodstream refers specifically to the unbound drug. When a drug is described as free, it indicates that it is not attached to plasma proteins and is available to exert its therapeutic effects. This unbound state is critical for pharmacological activity because only free drugs can cross biomembranes and reach their target sites in tissues, thus influencing their pharmacodynamic outcomes.

In contrast, drugs that are bound to plasma proteins are considered to be in a reservoir state where they are inactive and unable to interact with receptors or exert therapeutic effects. Inactive metabolites are products of drug metabolism that generally do not have pharmacological activity, and accumulated storage drugs refer to those that are sequestered in tissues and not readily available in the circulation for immediate use. These distinctions are essential for understanding drug behavior in the body and their therapeutic implications.