Plasma and urine pharmacokinetics of niacin and its metabolites from an extended-release niacin formulation.
OBJECTIVE
To characterize plasma and urine pharmacokinetics of niacin and its metabolites after oral administration of 2,000 mg of extended-release (ER) niacin in healthy male volunteers.


METHODS
Niacin ER was administered to 12 healthy male subjects following a low-fat snack. Plasma was collected for 12 h post dose and was analyzed for niacin, nicotinuric acid (NUA), nicotinamide (NAM) and nicotinamide-N-oxide (NNO). Urine was collected for 96 h post dose and analyzed for niacin and its metabolites, NUA, NAM, NNO, N-methylnicotinamide (MNA) and N-methyl-2-pyridone-5-carboxamide (2PY).


RESULTS
Mean niacin Cmax and AUC(0-t) values were 9.3 microg/ml and 26.2 microg x h/ml and were the highest of all analytes measured. Peak niacin and NUA levels occurred at 4.6 h (median) while tmax for NAM and NNO were 8.6 and 11.1 h, respectively. The mean plasma terminal half-life for niacin (0.9 h) and NUA (1.3 h) was shorter as compared to NAM (4.3 h). Urine recovery of niacin and metabolites accounted for 69.5% of the administered dose; only 3.2% was excreted as niacin. The highest recovery was for 2PY (37.9%), followed by MNA (16.0%) and NUA (11.6%). Mean half-lives for 2PY and MNA calculated in urine were 12.6 and 12.8 h, respectively.


CONCLUSIONS
Niacin was extensively metabolized following oral administration, and about 70% of the administered dose is recovered in urine in 96 h as niacin, NUA, MNA, NNO, NAM and 2PY. The plasma levels of the parent niacin were higher than its metabolites though only about 3% of the unchanged drug is recovered in urine.
Menon
R M
RM
Kos Pharmaceuticals, Weston, FL 33326, USA. menonrm2000@gmail.com
Adams
M H
MH
González
M A
MA
Tolbert
D S
DS
Leu
J H
JH
Cefali
E A
EA
D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006801:Humans; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D009539:Nicotinic Acids / Q000097:blood / Q000652:urine; D014815:Vitamins / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D009539:Nicotinic Acids; D014815:Vitamins; D009536:Niacinamide; D009525:Niacin; C016590:N(1)-methyl-4-pyridone-5-carboxamide; C037645:nicotinamide N-oxide; C002477:nicotinuric acid; C008472:N-methylnicotinamide