Impact of Pregnancy on the Pharmacokinetics and Metabolism of Nicotinamide in Humans

In pre‐eclampsia models, nicotinamide (NAM) has protective effects in pre‐eclampsia and is being evaluated as a therapeutic nutraceutical in clinical studies. NAM undergoes extensive hepatic metabolism by NAM N‐methyltransferase to methylnicotinamide (MNA), which is subsequently metabolized to methyl‐2‐pyridone‐5‐carboxamide (M2PY) by aldehyde oxidase. However, the pharmacokinetics of NAM and its major metabolites has never been studied in pregnant individuals. Blood samples were collected before and 1, 2, 4, 8, and 24 hours after single 1 g oral NAM dose in healthy pregnant (gestational age 24–33 weeks) and nonpregnant female volunteers (n = 6/group). Pooled urine was collected from 0 to 8 hours. NAM, MNA, and M2PY area under the concentration‐time curve (AUC) data were analyzed by noncompartmental analysis. No difference in the plasma AUC0→24 of NAM (median (25%–75%): 463 (436–576) vs. 510 (423, 725) μM*hour, P = 0.430) and its intermediate metabolite MNA (89.1 (60.4, 124.4) vs. 83.8 (62.7, 93.7) μM*hour, P = 0.515) was observed in pregnant and nonpregnant volunteers, respectively; however, the terminal metabolite M2PY AUC0 → 24 was significantly lower in pregnant individuals (218 (188, 254) vs. 597 (460, 653) μM*hour, P