Tissue-toxic effects of phosphatidylcholine/deoxycholate after subcutaneous injection for fat dissolution in rats and a human volunteer.

BACKGROUND: The safety of the lipodissolution procedure for the cosmetic treatment of fat is unknown. OBJECTIVES: The objective was to determine the subcutaneous tissue effects of phosphatidylcholine solubilized with deoxycholate (PC/DC) in rats and a human volunteer. METHODS: Rats were treated subcutaneously three times with 50, 300, or 600 microL of PC/DC formula on the abdomen in a chronic study (30 days). A human volunteer undergoing elective liposuction was similarly treated. Cell membrane lysis, cell viability, and histologic status were determined on fresh biopsies of subcutaneous fat from the injection sites. RESULTS: PC/DC dose-dependently reduced membrane integrity and cell viability. Histologic alterations induced by PC/DC included fibroplasia, bandlike fibrosis in the region of the cutaneous muscle, and partial muscle loss. The highest dose caused widespread fat necrosis, fat cyst formation, and necrotic changes of the walls of small blood vessels. Histologic sections of subcutaneous tissue from the human volunteer showed dose-dependent panniculitis, fat cysts, and vessel necrosis. DC (2.5%), tested for comparison in the rat, exerted membrane and histologic effects similar to those of PC/DC. Solvent controls caused negligible alterations. CONCLUSIONS: Injection lipolysis with PC/DC causes tissue fibrosis and necrosis of adipose and vascular tissues in rat and man, making the long-term safety of PC/DC for nonsurgical treatment of subcutaneous fat deposits uncertain.

Efficacy and safety of fluvastatin-extended release in hypercholesterolemic patients: morning administration is equivalent to evening administration.

BACKGROUND: Flexibility in the time of administration of statin therapy is likely to improve patient compliance. This study compared the efficacy and tolerability of morning and evening administration of the extended-release formulation of fluvastatin (fluvastatin XL). METHODS: In this prospective, double-blind, multicenter, multiple dose study, 236 patients with type IIa/b hypercholesterolemia were randomized to receive fluvastatin XL, 80 mg, in the morning or evening for 8 weeks. RESULTS: At 8 weeks, low-density lipoprotein cholesterol levels were reduced by 34.5 and 35.0% in the morning and evening treatment groups, respectively (p = 0.0118 for non-inferiority of morning administration). There were no statistically significant differences between the morning and evening treatment groups in the changes in total cholesterol (p = 0.56), high-density lipoprotein cholesterol (p = 0.21), triglycerides (p = 0.13), apolipoprotein B (p = 0.66) and apolipoprotein AI (p = 0.88) at 8 weeks. The frequency of adverse events was slightly lower in the morning treatment group compared with the evening treatment group (27.4 vs. 35.5%). CONCLUSIONS: The efficacy and safety profiles of fluvastatin XL are equivalent for morning and evening administration.