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Statin LDL cholesterol-lowering effect in hypercholesterolemia is described by model
Investigators in France note, "Statins are the most commonly prescribed agents for the treatment of hypercholesterolemia. This is due to their efficacy in reducing low-density lipoprotein cholesterol (LDL) level which is the primary goal of the treatment especially for patients with multiple risk factors or with established coronary heart diseases."
"The purpose of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model that describes the LDL-lowering process in patients with hypercholesterolemia treated with atorvastatin, fluvastatin or simvastatin," wrote D.W. Faltaos and colleagues at Pitie-Salpetriere University Hospital in Paris. "A total of 100 patients were studied retrospectively. They received atorvastatin (n=57), fluvastatin (n=26) or simvastatin (n=17). As no pharmacokinetic data were available, the absorption rate was fixed to 1/h and atorvastatin, simvastatin and fluvastatin elimination half-lives were fixed to 14, 2 and 2.5 h respectively."
"A total of 309 LDL levels were measured and the data were analyzed by nonmem v," they explained. "The time course of the LDL-lowering effect of statins was described by an indirect-response model with precursor (LDL synthesis, input rate Kin) and response (circulating LDL, input and output rates K) compartments. The following parameters were estimated: LDL input rate (Kin 0.14±0.015 g/L/day (mean±SD); inhibition fraction of Kin (INH) 0.21±0.017; and dose producing 50% increase of LDL removal (D50), 26±7.8, 1.3±0.48 and 15±5.25 mg for atorvastatin, simvastatin and fluvastatin, respectively."
Gender, bodyweight, age, calories/day, sugar/day, lipids/day, hyperlipidemia types and waist/hip circumference, renal and hepatic functions had no effect on the pharmacodynamic parameters," the scientists added. "The pharmacodynamic parameters for the three statins were accurately estimated."
The researchers concluded, "The PK/PD model developed successfully predicted the time course of the LDL-lowering effect of statins."