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 (PCOS) 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 to 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 to postpartum (342 ± 283 vs. 76 ± 92 mL/min, p < 0.01). Since creatinine is also a substrate of OCT2, MATE1, and MATE2-K, creatinine clearance likely overestimates filtration clearance while 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.
- efflux transporters (P-gp, BCRP, MRP, MATE, BSEP, etc)
- Uptake transporters (OATP, OAT, OCT, PEPT, MCT, NTCP, ASBT, etc.)
- The American Society for Pharmacology and Experimental Therapeutics