A -year-old man is hospitalized for treatment of methicillin-resistant *Staphylococcus aureus* (MRSA) osteomyelitis. For the past week, he has been receiving a continuous intravenous infusion of a novel antimicrobial agent at a rate of mg/hr. His renal and hepatic functions have remained stable. Routine therapeutic drug monitoring reveals a steady-state plasma concentration of mg/L.
The patient is now clinically stable and is being prepared for discharge to complete a prolonged course of therapy. The infectious disease specialist recommends transitioning the patient to an oral formulation of the same medication. To ensure adequate bone penetration for the remainder of the therapy, the specialist also recommends targeting a higher average steady-state plasma concentration of mg/L.
The oral formulation of this medication has a known bioavailability of (). The planned dosing interval for the oral regimen is every hours.
Assuming the patient's pharmacokinetic parameters remain constant, what oral dose (in mg) should be administered every hours to achieve the new target concentration?
Answer: 800 mg
Answer
Next, to achieve a new target steady-state concentration () of mg/L, the new required systemic delivery rate must be calculated: .
Since the new regimen will be administered intermittently every hours ( hr), the total systemic exposure required per interval is .
Finally, because the oral formulation is only bioavailable (), the administered oral dose must be larger than the required systemic dose to account for first-pass metabolism and incomplete absorption. The maintenance dose equation is . Substituting the values yields .