Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Clarithromycin/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Pyrimidines/metabolism , Pyrimidines/therapeutic use , Pyrimidines/pharmacokinetics , Rhabdomyolysis/chemically induced , Sulfonamides/metabolism , Sulfonamides/therapeutic use , Sulfonamides/pharmacokinetics , Fatty Acids, Monounsaturated/metabolism , Fatty Acids, Monounsaturated/therapeutic use , Fatty Acids, Monounsaturated/pharmacokinetics , Pravastatin/metabolism , Pravastatin/therapeutic use , Pravastatin/pharmacokinetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism , Organic Anion Transporters , Organic Anion Transporters, Sodium-Independent/antagonists & inhibitors , Liver-Specific Organic Anion Transporter 1 , Drug Interactions , Acute Kidney Injury/chemically induced , Rosuvastatin Calcium , Fluorobenzenes/metabolism , Fluorobenzenes/therapeutic use , Fluorobenzenes/pharmacokinetics , Solute Carrier Organic Anion Transporter Family Member 1B3 , Fluvastatin , Hyperkalemia/chemically induced , Indoles/metabolism , Indoles/therapeutic use , Indoles/pharmacokineticsABSTRACT
The purpose of this study is to determine the population pharmacokinetics of 3 statins after oral dosing. This was achieved by simultaneous data fitting of 101 different individuals from three studies: 25 subjects for pravastatin, 40 subjects for simvastatin and 36 subjects for atorvastatin. Each study was fitted separately. Plasma profiles were best characterized by 1 -compartment model for pravastatin, 2-compartment model for simvastatin, and 3 -compartment model for atorvastatin. The criteria used for model building involved the examination of the fitted cuves, the improvement in objective function and statistical tests: Akaike test, Schwarz test and log likelihood test; and examining the improvement in residual plots. The elimination rate constant and clearance values for pravastatin is higher than simvastatin and higher than atorvastatin which is in agreement with models used. The variability, as indicated by population coefficient of variation, is generally higher than 30% rendering them highly variable drugs