This charge-based phenomenon can be illustrated with the use of lidocaine (pKa 7.8). Note that at low pH the predominant fraction of a basic drug is ionized conversely, the predominant fraction of an acidic is nonionized. The relationship between the pKa of an acidic (AH) and a basic (B) drug and the pH of the biological medium. The pKa of a drug is defined as that pH of a biological medium at which 50% of the drug is protonated (i.e., electrically neutral) and 50% is deprotonated (i.e., electrically negative). Since only the nonpolar faction of a drug can diffuse across biological membranes, net diffusion of acidic and basic drugs is affected by a charge-based phenomenon known as pH trapping, which depends on a drug’s acid dissociation constant (pKa) and the pH of the biological environment (Figure 6). However, passive diffusion is ineffective for the transport of large, polar molecules. Nonetheless, most small, nonpolar, lipophilic molecules are able to diffuse through lipid bilayer membranes along the concentration gradient by passive diffusion until equilibrium is reached. The membrane’s semipermeable lipid bilayer presents the major barrier to drugs. To elicit an effect on its target, a drug must be absorbed and then distributed to its binding site before being metabolized and excreted.Īll human cells have a lipid bilayer cytoplasmic membrane consisting mainly of phospholipids, sterols, and glycolipids.
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