Beth R. (58 kg, 63 years old) is suffering from symptomatic ventricular arrhythmia. She will be started on an oral multiple-dose regimen with the antiarrhythmic mexiletine. The population average values of mexiletine for clearance and volume of distribution are Cl = 0.5 L/h/kg and V = 6 L/kg, respectively. Although a therapeutic range of 0.5– 2 mg/L has been described, avoiding large peak-to- trough fluctuations is recommended. The available oral dosage forms are 150, 200, and 250 mg capsules with an
Beth R. (58 kg, 63 years old) is suffering from symptomatic ventricular arrhythmia. She will be started on an oral multiple-dose regimen with the antiarrhythmic mexiletine. The population average values of mexiletine for clearance and volume of distribution are Cl = 0.5 L/h/kg and V = 6 L/kg, respectively. Although a therapeutic range of 0.5– 2 mg/L has been described, avoiding large peak-to- trough fluctuations is recommended. The available oral dosage forms are 150, 200, and 250 mg capsules with an oral bioavailability of 0.9%. Design an appropriate and practical oral-dosing regimen that keeps the plasma concentrations at an average concentration of approximately 1 mg/L, with a peak-to-trough fluctuation of less than or equal to 100% (between 0.75 and 1.5 mg/L). What dosing regimen should be used?
A. 150 mg every 6 hours
B. 200 mg every 6 hours
C. 200 mg every 8 hours
D. 250 mg every 8 hours
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