mk-0524 and Hypophosphatemia

Niacin administration lowers the marked hyperphosphatemia that is characteristic of renal failure. We examined whether niacin administration also reduces serum phosphorus concentrations in patients who have dyslipidemia and are free of advanced renal disease.. We performed a post hoc data analysis of serum phosphorus concentrations that had been determined serially (at baseline and weeks 4, 8, 12, 18, and 24) among 1547 patients who had dyslipidemia and were randomly assigned in a 3:2:1 ratio to treatment with extended release niacin (ERN; 1 g/d for 4 weeks and dose advanced to 2 g/d for 20 weeks) combined with the selective prostaglandin D2 receptor subtype 1 inhibitor laropiprant (L; n = 761), ERN alone (n = 518), or placebo (n = 268).. Repeated measures analysis revealed that ERN-L treatment resulted in a net mean (95% confidence interval) serum phosphorus change comparing ERN-L with placebo treatment of -0.13 mmol/L (-0.15 to -0.13 mmol/L; -0.41 mg/dl [-0.46 to -0.37 mg/dl]). These results were consistent across the subgroups defined by estimated GFR of <60 or > or =60 ml/min per 1.73 m(2), a serum phosphorus of >1.13 mmol/L (3.5 mg/dl) versus < or =1.13 mmol/L (3.5 mg/dl), the presence of clinical diabetes, or concomitant statin use.. We have provided definitive evidence that once-daily ERN-L treatment causes a sustained 0.13-mmol/L (0.4-mg/dl) reduction in serum phosphorus concentrations, approximately 10% from baseline, which is unaffected by estimated GFR ranging from 30 to > or =90 ml/min per 1.73 m(2) (i.e., stages 1 through 3 chronic kidney disease).

Topics: Aged; Biomarkers; Calcium; Chronic Disease; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Dyslipidemias; Female; Glomerular Filtration Rate; Humans; Hyperphosphatemia; Hypolipidemic Agents; Hypophosphatemia; Indoles; Kidney Diseases; Male; Middle Aged; Niacin; Phosphorus; Receptors, Immunologic; Receptors, Prostaglandin; Severity of Illness Index; Time Factors

Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Dyslipidemias; Humans; Hypolipidemic Agents; Hypophosphatemia; Indoles; Kidney Failure, Chronic; Lipids; Niacin; Treatment Outcome