Drug Safety Considerations, Part 1: Absorption

Pharmacokinetics, the science of how a drug becomes available for activity in the body, encompasses four primary variables: Absorption, Distribution, Metabolism and Elimination.  Each of these is impacted by individual variation and impactful to the ultimate clinical and/or adverse effect of a drug.

Absorption generally refers to the process by which an administered drug reaches the systemic circulation.  The physical and chemical properties of individual medications are critical factors in whether and to what extent a drug will be absorbed.  When absorption following oral administration is evaluated, the term bioavailability is used to represent the fraction of drug reaching the circulation compared to an intravenously administered dose.  A drug demonstrating excellent bioavailability approaching 100% would be expected to achieve similar serum concentrations when given orally versus intravenously.  Drugs with reduced or absent bioavailability would have limited or no potential for systemic absorption.  Protein based molecules such as insulin are prone to degradation in the acid medium of the stomach, and drugs with large molecular structures such as vancomycin are unlikely to cross from the intestines into the bloodstream.  Both examples characterize limited bioavailability, making them poor candidates for oral administration.

Human factors can also affect drug absorption.   Changes in the acidity of the gastric environment can lead to reduced – and in some cases, enhanced – bioavailability.  Infants are known to have a less acidic gastric environment during early development, changing their absorption capacity for certain medications.  The elderly often develop diminished gastric acid production, with similar impacts on bioavailability.

Drug or food interactions may also affect drug absorption.  Acid suppressive agents like proton pump inhibitors (pantoprazole, Protonix, omeprazole, Prilosec, lansoprazole, Prevacid, esomeprazole, Nexium, among others) derive their clinical benefit from reduced gastric acidity, but that same reduction in acidity can impede or enhance the absorption of other drugs sensitive to gastric acidity levels.   Antacids, calcium supplements and dairy products may experience physical interactions with other medications, rendering reduced absorption – and ultimately, reduced clinical effect – of the target drug.

The potential impact of topically administered drugs also warrants consideration.  Although unlikely when used as prescribed, some medications applied to the skin may reach the circulation and have unintended systemic effects.  Similarly, excessive administration of a topical medication (either by prescribing/compounding error or improper amount/frequency of application) can have unwanted local or systemic adverse effects.

A medication based litigation case would benefit from a critical evaluation by a qualified expert whose assessment would include the spectrum of potential contributing or confounding factors applicable to the case, including these drug safety considerations.

Upcoming:  Drug Safety Considerations – Distribution