Assessment of potential pharmacokinetic interactions of ezetimibe/simvastatin and extended-release niacin tablets in healthy subjects.

BACKGROUND: Efforts to lower plasma lipid levels sometimes require multiple agents with different mechanisms of action to achieve results specified by national treatment guidelines. METHODS: This was an open-label, randomized, three-period, multiple-dose crossover study that assessed the potential for pharmacokinetic interaction between extended-release niacin and ezetimibe/simvastatin and their major metabolites. Eighteen adults received three randomized treatments: (A) extended-release (ER) niacin 1000 mg/day for 2 days, followed by 2000 mg/day for 5 days; (B) ezetimibe/simvastatin 10 mg/20 mg/day; (C) coadministration of Treatments A and B. Treatments were given once a day after a low fat breakfast for a total of 7 days, with a 7-day inter-dose period. RESULTS: There were small (mean ≤35%) increases in drug exposure for all analytes after coadministration of ER niacin and ezetimibe/simvastatin 10 mg/20 mg. The least-square mean between treatment C(max) (maximum plasma concentration) ratios (×100) were 97, 98, and 109% for ezetimibe, simvastatin and niacin, respectively. The corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 99, 118, and 110%. The AUC((0-24)) (area under the plasma concentration-time curve from time zero to 24 h after dosing) ratios for ezetimibe, simvastatin, and niacin were 109, 120, and 122%, respectively, and the corresponding ratios for total ezetimibe, simvastatin acid, and nicotinuric acid were 126, 135 and 119%. CONCLUSION: There is a small pharmacokinetic drug interaction between ER niacin and ezetimibe/simvastatin and although this is not considered to be clinically significant, the concomitant use of these drugs should be appropriately monitored, especially during the niacin titration period.

An episode-based framework for analyzing health care expenditures: an application of reward renewal models.

OBJECTIVE: To illustrate an episode-based framework for analyzing health care expenditures based on reward renewal models, a stochastic process used in engineering for describing processes that cycle on and off with "rewards" (or costs) occurring at the end of each cycle. DATA SOURCES/STUDY SETTING: Data used in the illustration were collected as part of an evaluation of a national initiative to improve mental health services for children and youth. Participants were enrolled in a longitudinal study at a demonstration site and in a comparison community between 1997 and 1999. The illustration involves analyses of mental health expenditures at the two sites and of the dynamics of service use behind those expenditures. DATA COLLECTION/EXTRACTION METHODS: Services data were derived from management information systems as well as patient records at inpatient facilities in the two communities. These data cover services received between 1997 and 2003. The analysis focuses on the year following study entry. PRINCIPAL FINDINGS: Between-site differences in expenditures reflect complex between-site differences in the timing of service use. In particular, children at the demonstration stayed in treatment longer but were less likely to return for treatment later. In contrast, children at the comparison site experienced substantially less continuity of care. Costs per day of treatment within an episode were comparable at the two sites. CONCLUSIONS: Reward renewal models offer a promising means for integrating research on service episodes and the dynamics of service use with that on health care expenditures.