Journal
DRUG METABOLISM AND DISPOSITION
Volume 45, Issue 3, Pages 325-329Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.116.073841
Keywords
-
Categories
Funding
- National Institutes of Health (NIH) Eunice Kennedy Shriver National Institute of Child Health & Human Development [U10HD047892]
- NIH National Center for Advancing Translational Sciences through the Clinical and Translational Science Awards Program (CTSA) [UL1TR000423]
- NIH National Institute of General Medical Sciences [T32GM007750]
Ask authors/readers for more resources
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 6 106 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). Becausecreatinine isalsoasubstrateof 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available