Pregnancy Increases the Renal Secretion of N 1 -methylnicotinamide, an Endogenous Probe for Renal Cation Transporters, in Patients Prescribed Metformin.

Autor: Bergagnini-Kolev MC; Department of Pharmaceutics (M.C.B.-K.,Y.S.L.), Department of Obstetrics and Gynecology (M.F.H., T.R.E.), and Department of Pharmacy (M.F.H.), University of Washington, Seattle, Washington., Hebert MF; Department of Pharmaceutics (M.C.B.-K.,Y.S.L.), Department of Obstetrics and Gynecology (M.F.H., T.R.E.), and Department of Pharmacy (M.F.H.), University of Washington, Seattle, Washington., Easterling TR; Department of Pharmaceutics (M.C.B.-K.,Y.S.L.), Department of Obstetrics and Gynecology (M.F.H., T.R.E.), and Department of Pharmacy (M.F.H.), University of Washington, Seattle, Washington., Lin YS; Department of Pharmaceutics (M.C.B.-K.,Y.S.L.), Department of Obstetrics and Gynecology (M.F.H., T.R.E.), and Department of Pharmacy (M.F.H.), University of Washington, Seattle, Washington yvonlin@uw.edu.
Jazyk: angličtina
Zdroj: Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2017 Mar; Vol. 45 (3), pp. 325-329. Date of Electronic Publication: 2017 Jan 09.
DOI: 10.1124/dmd.116.073841
Abstrakt: N 1 -methylnicotinamide (1-NMN) has been investigated as an endogenous probe for the renal transporter activity of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 and 2-K (MATE1 and MATE2-K). As pregnancy increased the renal secretion of metformin, a substrate for OCT2, MATE1, and MATE2-K, we hypothesized that the renal secretion of 1-NMN would be similarly affected. Blood and urine samples collected from women prescribed metformin for type 2 diabetes, gestational diabetes, and polycystic ovarian syndrome during early, mid, and late pregnancy ( n = 34 visits) and postpartum ( n = 14 visits) were analyzed for 1-NMN using liquid chromatography-mass spectrometry. The renal clearance and secretion clearance, using creatinine clearance to correct for glomerular filtration, were estimated for 1-NMN and correlated with metformin renal clearance. 1-NMN renal clearance was higher in both mid (504 ± 293 ml/min, P < 0.01) and late pregnancy (557 ± 305 ml/min, P < 0.01) compared with postpartum (240 ± 106 ml/min). The renal secretion of 1-NMN was 3.5-fold higher in mid pregnancy (269± 267, P < 0.05) and 4.5-fold higher in late pregnancy compared with postpartum (342 ± 283 versus 76 ± 92 ml/min, P < 0.01). Because creatinine is also a substrate of OCT2, MATE1, and MATE2-K, creatinine clearance likely overestimates filtration clearance, whereas the calculated 1-NMN secretion clearance is likely underestimated. Metformin renal clearance and 1-NMN renal clearance were positively correlated (r s = 0.68, P < 0.0001). 1-NMN renal clearance increases during pregnancy due to increased glomerular filtration and net secretion by renal transporters.
(Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze: MEDLINE
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