Curves D and E represent concentrations after regular bolus administration of the same dose of an antibiotic to the same patient  at different points of time. What pharmacokinetic changes are noticed? List two clinical conditions that could explain the difference between E and D?

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College Answer

a)  PK changes – Increased plasma concentrations with E for the same dose indicating reduced clearance and increased half life.

b)    Hepatic dysfunction , renal dysfunction

Discussion

This was easy marks. In the instance E, the clearance rate is decreased. You can see that with the first dose: even though the initial plasma concentration is the same after the first dose, curve D has a steeper slope, which suggests more rapid clearance (i.e. the concentration falls faster). Intermittent dosing in curve E results in a gradual increase of plasma concentration, with a higher steady-state concentration.

Two clinical conditions which might result in such a situation are hepatic impairment and renal impairment.