Flow cytometric assessment of effects of fluvastatin on low-density lipoprotein receptor activity in stimulated T-lymphocytes from patients with heterozygous familial hypercholesterolemia

To test the effects of fluvastatin on low-density lipoprotein (LDL) recepto r activity in patients with heterozygous familial hypercholesterolemia, the authors measured LDL receptor activity in stimulated T-lymphocytes prepare d from 34 patients before and after treatment with 40 mg fluvastatin daily for 32 weeks. Maximally induced pretreatment LDL receptor activities did no t correlate with pretreatment plasma cholesterol levels or with changes in plasma cholesterol levels during treatment, and there were no significant c hanges in LDL receptor activity during treatment. Barring methodological pr oblems, two explanations are possible. Insofar that LDL receptor activity i n lymphocytes reflects LDL receptor activity in the liver, the results sugg est that the primary response to treatment with fluvastatin in heterozygous familial hypercholesterolemia (FH) patients is not enhanced LDL receptor a ctivity. Alternatively, fluvastatin increases LDL receptor activity in hepa tocytes but has little effect on receptor-dependent lipoprotein catabolism in extrahepatic tissues in vivo. Journal of Clinical Pharmacology, 2000;40: 421-429 (C)2000 the American College of Clinical Pharmacology.