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  • Title: CYP3A4 Induction by Rifampin: An Alternative Pathway for Vitamin D Inactivation in Patients With CYP24A1 Mutations.
    Author: Hawkes CP, Li D, Hakonarson H, Meyers KE, Thummel KE, Levine MA.
    Journal: J Clin Endocrinol Metab; 2017 May 01; 102(5):1440-1446. PubMed ID: 28324001.
    Abstract:
    CONTEXT: The P450 enzyme CYP24A1 is the principal inactivator of vitamin D metabolites. Biallelic loss-of-function mutations in CYP24A1 are associated with elevated serum levels of 1,25-dihydroxyvitamin D3 with consequent hypercalcemia and hypercalciuria and represent the most common form of idiopathic infantile hypercalcemia (IIH). Current management strategies for this condition include a low-calcium diet, reduced dietary vitamin D intake, and limited sunlight exposure. CYP3A4 is a P450 enzyme that inactivates many drugs and xenobiotics and may represent an alternative pathway for inactivation of vitamin D metabolites. OBJECTIVE: Our goal was to determine if rifampin, a potent inducer of CYP3A4, can normalize mineral metabolism in patients with IIH due to mutations in CYP24A1. METHODS: We treated two patients with IIH with daily rifampin (10 mg/kg/d, up to a maximum of 600 mg). Serum calcium, phosphorus, parathyroid hormone (PTH), liver, and adrenal function and vitamin D metabolites, as well as urinary calcium excretion, were monitored during treatment of up to 13 months. RESULTS: Prior to treatment, both patients had hypercalcemia, hypercalciuria, and nephrocalcinosis with elevated serum 1,25-dihydroxyvitamin D3 and suppressed serum PTH. Daily treatment with rifampin was well tolerated and led to normalization or improvement in all clinical and biochemical parameters. CONCLUSION: These observations suggest that rifampin-induced overexpression of CYP3A4 provides an alternative pathway for inactivation of vitamin D metabolites in patients who lack CYP24A1 function.
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