The drug distribution process within the human body is a complex interplay of various physicochemical properties inherent to the drugs. These properties, including molecular size, ionization degree, partition coefficient, and stereochemical nature, significantly impact how drugs permeate biological membranes to reach their target tissues.

Small molecules with a molecular weight below 500 to 600 Daltons can easily pass through the capillary membrane, gaining access to different tissues. Larger molecules, in contrast, require specialized transport systems to traverse biological barriers effectively.

A crucial determinant in drug distribution is whether the drug is unionized and lipophilic or ionized, polar, and hydrophilic. Due to their chemical characteristics, unionized and lipophilic drugs can rapidly cross cell membranes, whereas ionized, polar, and hydrophilic drugs face challenges in membrane permeation.

The blood pH plays a pivotal role in drug ionization. Changes in blood pH resulting from conditions like acidosis or alkalosis can alter the ionization state of drugs, thereby impacting their intracellular concentration. An example of this phenomenon occurs in the treatment of barbiturate poisoning. Through the induction of alkalosis using sodium bicarbonate, the drug is driven out of the central nervous system and excreted more efficiently through urine, aided by increased ionization.

The distribution of polar drugs is influenced by their effective partition coefficient. For example, thiopental, a weak acid with a high partition coefficient, distributes more rapidly than salicylic acid, a strong acid with a lower coefficient. This discrepancy demonstrates how the partition coefficient directly affects the speed and efficiency of drug distribution in tissues.

A drug's stereochemical nature, particularly concerning interactions with macromolecules such as proteins, can further modulate its distribution within the body. These interactions can determine how drugs bind, move, and exert their effects, adding another layer of complexity to the intricate drug distribution process across biological membranes.