Corticosteroid-induced mania prepare for the unpredictable

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Dofetilide is administered orally. The terminal half-life is approximately 10 hours, and steady state plasma concentrations are attained within 2 to 3 days. Plasma protein binding is 60% to 70%, and is independent of plasma concentration and renal function. The volume of distribution is about 3 L/kg. Metabolites are formed by N-dealkylation and N-oxidation. There are no quantifiable metabolites circulating in plasma, but five metabolites have been identified in the urine. In vitro studies with human hepatic microsomes show that dofetilide is metabolized to some extent by CYP3A4, although it has a low affinity for this isoenzyme. Approximately 80% of a single dose is excreted in urine, of which approximately 80% is excreted as unchanged dofetilide and the remaining 20% consists of inactive or minimally active metabolites. Renal elimination involves both glomerular filtration as well as active tubular secretion via the cation transport system, a process that can be inhibited by cimetidine and ketoconazole. Use is contraindicated for renal cation transport inhibitors.
 
Affected cytochrome P450 isoenzymes: CYP3A4
Dofetilide is a substrate of CYP3A4, although it has a low affinity for this enzyme. Erythromycin, a potent CYP3A4 inhibitor, significantly increases dofetilide plasma concentrations. Dofetilide does not inhibit CYP3A4 or other cytochrome P450 isoenzymes. 

Corticosteroid-induced mania prepare for the unpredictable

corticosteroid-induced mania prepare for the unpredictable

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