Effect of intravenous iron supplementation on hepatic cytochrome P450 3A4 activity in hemodialysis patients: a prospective, open-label study

Clinical Therapeutics
Amy Barton PaiLingtak-Neander Chan

Abstract

Cytochrome P450 (CYP) 3A4 is an enzyme with activity dependent on the reduction of heme iron that is responsible for the metabolism of many drugs. CYP3A4 activity is reduced in hemodialysis (HD) patients and thus may be related to functional iron deficiency. The purpose of this study was to investigate the effect of IV iron supplementation on hepatic is CYP3A4 activity in HD patients. This prospective, open-label study was conducted in 12 iron-deficient (transferrin saturation <20% or ferritin <100 ng/L) HD patients on stable medication regimens. To probe for hepatic CYP3A4 activity, an erythromycin breath test (ERMBT) was administered before and after 1 g IV iron sucrose (administered as a 100-mg dose [20 mg/mL]), at each of 10 consecutive HD sessions). CYP3A4 activity was estimated by the percentage of administered (14)C exhaled in a single-breath collection after the test dose of erythromycin underwent demethylation by CYP3A4. The ERMBT was also administered to 7 age-, sex-, and race-matched healthy controls. Twelve HD patients (6 Hispanic, 3 white, 3 Native American; 8 men, 4 women; mean [SEM] age, 56.2 [5.0] years; mean [SEM] weight, 77.0 [5.6] kg; and 7 controls (4 men, 3 women; mean [SEM] age, 51.3 [5.0] years; mean [SEM...Continue Reading

Citations

Aug 24, 2010·Advances in Chronic Kidney Disease·Nicole R PinelliSarah Tomasello
Sep 12, 2020·Archives of Toxicology·Linn VossHolger Sieg

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