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

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Bergagnini-Kolev MC, Hebert MF, Easterling TR, Lin YS

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

Drug Metab Dispos. 2017 Mar;45(3):325-329. doi: 10.1124/dmd.116.073841. Epub 2017 Jan 9.

PubMed ID
28069720 [ View in PubMed
]
Abstract

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 (rs = 0.68, P < 0.0001). 1-NMN renal clearance increases during pregnancy due to increased glomerular filtration and net secretion by renal transporters.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
N-methylnicotinamideMultidrug and toxin extrusion protein 2ProteinHumans
Unknown
Substrate
Details