Pharmacokinetics and dose recommendations of Niaspan® in chronic kidney disease and dialysis patients.
BACKGROUND
Niaspan® is an extended-release formulation of nicotinic acid with improved tolerability compared with the immediate-release and sustained-release formulations. It is used to treat hypertriglyceridaemia with low high-density lipoprotein levels. This type of dyslipidaemia frequently appears in patients with chronic kidney disease (CKD). Dose recommendations for these patients are not available because pharmacokinetic data are missing. The present study was performed to analyse the pharmacokinetics of prolonged-release nicotinic acid in CKD and in dialysis patients to derive dose recommendations.


METHODS
Ten dialysis patients and eight patients with CKD were enrolled in a prospective, three-period, open-label pharmacokinetic study. They received in the first week 500 mg Niaspan® per day, in the second week 1000 mg/day and in the third week 1500 mg/day. On the fourth day of every treatment unit, 11 plasma samples were collected for 24 h post-dose and analysed for nicotinic acid (NA) and its metabolites nicotinamide and nicotinuric acid (NUA).


RESULTS
Median plasma NA concentrations in subjects with CKD were obviously higher than in dialysis patients, but not higher than reported in patients without renal impairment. t(max) of NA were on average 0.75 h in dialysis patients and 3.0 h in CKD patients and, therefore, especially for dialysis patients, clearly shorter than expected for extended-release formulations. It is particularly noticeable that the AUC, C(max) and t(1/2) of the metabolite NUA are significantly higher in dialysis patients in comparison to CKD patients. This may indicate that the dialysis was not effective in removing this metabolite. However, there was no correlation between the incidence of flush and the concentration of NUA. Another possibility could be a drug-drug interaction with omeprazole via CYP450 enzymes.


CONCLUSIONS
These data suggest that no dose adjustment of Niaspan® is necessary in patients with renal impairment. Despite an extended-release formulation of NA, we could not detect a delay in t(max) especially in dialysis patients. We found no correlation between the incidence of flush and the NUA concentration. Furthermore, there were hints of an interaction with omeprazole.
Reiche
Ines
I
Institute of Clinical Pharmacology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, Magdeburg, Germany.
Westphal
Sabine
S
Martens-Lobenhoffer
Jens
J
Tröger
Uwe
U
Luley
Claus
C
Bode-Böger
Stefanie M
SM
D000368:Aged; D002908:Chronic Disease; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009536:Niacinamide / Q000032:analysis; D009539:Nicotinic Acids / Q000032:analysis; D011446:Prospective Studies; D006435:Renal Dialysis; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
D000960:Hypolipidemic Agents; D009539:Nicotinic Acids; D009536:Niacinamide; D009525:Niacin; C002477:nicotinuric acid