TY - JOUR T1 - Pregnancy Increases the Renal Secretion of N<sup>1</sup>-methylnicotinamide, an Endogenous Probe for Renal Cation Transporters, in Patients Prescribed Metformin JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 325 LP - 329 DO - 10.1124/dmd.116.073841 VL - 45 IS - 3 AU - Mackenzie C. Bergagnini-Kolev AU - Mary F. Hebert AU - Thomas R. Easterling AU - Yvonne S. Lin Y1 - 2017/03/01 UR - http://dmd.aspetjournals.org/content/45/3/325.abstract N2 - N1-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 &lt; 0.01) and late pregnancy (557 ± 305 ml/min, P &lt; 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 &lt; 0.05) and 4.5-fold higher in late pregnancy compared with postpartum (342 ± 283 versus 76 ± 92 ml/min, P &lt; 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 &lt; 0.0001). 1-NMN renal clearance increases during pregnancy due to increased glomerular filtration and net secretion by renal transporters. ER -