Sex and Racial Differences in Pharmacological Response: Effect of Route of Administration and Drug Delivery System on Pharmacokinetics

Mechanistic investigations into the physiological and biochemical differences between patients have only recently begun to help explain what was previously categorized as "intersubject variability." Additional factors, including the particular drug formulation or delivery system, have been implicated in observed sex-based and race-based differences in pharmacokinetic response. Drug absorption following intramuscular injection can be highly variable if the injection is mistakenly placed in the overlying tissues, a situation that is more likely to occur in women than men. Slower gastric emptying in women can significantly delay the onset of effectiveness of enteric-coated dosage forms, and differences in gastric pH can affect the drug solubility and dissolution rate. Slower drug release rates designed into many extended release dosage forms interact with the differential locations and populations of intestinal and hepatic transporters and metabolizing enzymes to cause significant sex-based and race-based differences in plasma drug concentrations. Increased efforts to identify and understand the interplay of an individual's physiological makeup, dietary intake, environment, and the drug products he or she uses are needed to be able to provide optimal drug therapy regimens to each patient.