If a patient on isoniazid therapy has acid reflux, what pharmacokinetic issue is likely relevant?

• A. Decreased absorption of isoniazid
• B. Increased absorption of isoniazid
• C. No effect
• D. Increased metabolism

Answer: (A)

Drug absorption depends on the drug’s ionization state, which is determined by the pH of the surrounding environment. Isoniazid is a weak base, so in a more acidic stomach environment (acid reflux) it becomes more ionized and less able to cross the gut wall. This reduced ability to permeate the intestinal lining lowers the fraction that enters the bloodstream, meaning decreased absorption and lower systemic exposure. Metabolism or no effect aren’t the primary issues here, because the acid environment mainly alters how much drug gets absorbed rather than how quickly it’s metabolized. So the pharmacokinetic issue most likely relevant is decreased absorption due to increased ionization in acidic gastric conditions.