Effect of the rate of niacin administration on the plasma and urine pharmacokinetics of niacin and its metabolites.

The metabolic profile of niacin is influenced by the rate of niacin administration. This study characterizes the effect of administration rate on the pharmacokinetics of niacin and its metabolites. Twelve healthy males were enrolled in an open-label, dose-rate escalation study and received 2000 mg niacin at 3 different dosing rates. Plasma was analyzed for niacin, nicotinuric acid, nicotinamide, and nicotinamide-N-oxide. Urine was analyzed for niacin and the metabolites nicotinuric acid, nicotinamide, nicotinamide-N-oxide, N-methylnicotinamide, and N-methyl-2-pyridone-5-carboxamide. C(max) and AUC(0-t) for niacin and nicotinuric acid increased with an increase in dosing rate. The changes observed in plasma nicotinamide and nicotinamide-N-oxide parameters, however, did not correlate to dosing rate. The total amount of niacin and metabolites excreted in urine was comparable for all 3 treatments. However, with the increase in dosing rate, urine recovery of niacin and nicotinuric acid showed a significant increase, whereas N-methyl-2-pyridone-5-carboxamide and N-methylnicotinamide showed a significant decrease.

Pharmacokinetics of eplerenone after single and multiple dosing in subjects with and without renal impairment.

The influence of renal impairment on the pharmacokinetics of eplerenone following single and multiple dosing was evaluated. Subjects (n = 64) were stratified based on creatinine clearance values as follows: renal impairment (mild, moderate, severe), hemodialysis, and normal matches. Subjects received a single dose of eplerenone 100 mg on day 1 and then received 100 mg once daily on days 3 to 8. There were no statistically significant differences between any of the renal impairment groups and their matched-normal groups for area under the curve (AUC), C(max), or CL/F or CL/F/WT following either single or multiple dosing (P > or = .093). The inactive metabolite and inactive ring-opened form displayed greater AUCs in renal impairment. Hemodialysis removed approximately 10% of the eplerenone dose. Eplerenone 100 mg once daily was well tolerated in all groups. Considering that renal function had no significant effects on eplerenone CL/F and that eplerenone metabolites are inactive, no dose adjustment appears necessary in patients with renal dysfunction.