Older Persons & Drugs: race, gender, and age effects

Jewish Home Of San Francisco, San Francisco CA

Investigators

Linked publications, trials & patents

Abstract

This project is a randomized double-blind placebo-controlled clinical investigation of the effects of supplemental vitamin D on atorvastatin and lipid concentrations in atorvastatin-treated patients. The request is based on unexpected findings from open label investigations of vitamin D that showed lower atorvastatin concentrations during vitamin D co-administration in a small group of patients. Counter to expectations, cholesterol levels were lower when vitamin D was co-administered with atorvastatin despite lower total active atorvastatin concentrations. This finding strongly suggests a role for vitamin D in lipid metabolism. Lower atorvastatin concentrations during vitamin D administration might also be associated with fewer concentration-related adverse effects such as myopathy. Randomized double-blind placebo controlled studies of 1000 IU/day vitamin D2, D3 or placebo in both atorvastatin-treated patients and non-statin treated people were initiated to investigate vitamin D, atorvastatin, and lipid responses. Studies were terminated upon discovery that the vitamin D formulations used (from UCSF Drug Products Service Laboratory) were out of labelled specifications and had degraded over time such that dosage administered was uncertain and likely to be in the "no effect" range. Unfortunately, the studies must be repeated. We propose to investigate effects of 1000 or 2000 IU/day vitamin D3 on complete lipid profiles (directly measured cholesterol subfractions, lipoproteins and non-cholesterol sterols (HDL, LDL, VLDL, IDL, and Lp(a), HDL2, HDL3, and LDL1-LDL4, LDL subclass pattern (A, A/B or B) and remnant cholesterol) and vitamin D levels (D3 and D2 specific 25-OH) at baseline and after 6 and 12 weeks of vitamin D. Atorvastatin concentration vs. time relationships will be determined at baseline and after 12 weeks vitamin D. We will titrate vitamin D from 1000 to 2000 IU/day to achieve 25-OH D levels >25 ng/mL. Exploratory measures of muscle strength, as well as measurements will be made. If vitamin D alters clearance of atorvasastatin, it may alter clearance of the many CYP3A substrates administered therapeutically. If vitamin D can reduce lipids or lower doses of statins or statin side effects, a new approach to the treatment of lipid disorders will be found.