MEDizzy - A 60-year-old man with rheumatoid arthritis will be started

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General pharmacology

A 60-year-old man with rheumatoid arthritis will be started on a non-steroidal anti-inflammatory drug to suppress joint inflammation. Published pharmacokinetic data for this drug include Bioavailability (F): 1.0 (100%) Plasma half-life (t1/2): 0.5 h Volume of distribution (Vd): 45 L For this drug, it is important to maintain an average steady-state concentration 2.0 mcg/mL in order to ensure adequate and continued anti-inflammatory activity. The drug will be given (taken) every 4 h. What dose will be needed to obtain an average steady-state drug concentration of 2.0 mcg/mL?

ExplanationHere is how you solve the problem. Note: It’s easy to be misled by inconsistent use of units of measurement (mcg vs. mg, mL vs. L), so be sure you convert units as necessary. First calculate the drug’s elimination rate constant: ke = 0.693/t1/2 or ke = 0.693/0.5 h = 1.386/h Then calculate the clearance: Cl = ke × Vd, or . . . . Cl = 1.386/h × 45 L, which equals 62.37 L/h, or 62,370 mL/h Recall that Cave = (F/Cl) × (Dose/t), where t represents the dosing interval (time; given as 4 h). Rearrange to solve for the dose. Dose = (Cave × Cl × t)/F, or Dose = [(2 mcg/mL) × (62,370 mL/h) × 4 h]/1.0 Thus, Dose = 499,000 mcg, or 499 mg (close enough to 500 mg).