Rate of low-density lipoprotein cholesterol and apolipoprotein B changes on initiation and discontinuation of atorvastatin treatment.
In a clinical trial, the changes in LDL cholesterol and in total apolipoprotein B with time were analyzed using a one-compartment model with constant input rate and first-order elimination rate constant after the initiation and discontinuation of treatment with atorvastatin. After initiation of treatment, input rate for total apoplipoprotein B (21 mg/dL/day) and elimination rate constants for both total apoplipoprotein B (0.36 days-1) and low-density lipoprotein (LDL) cholesterol (0.24 days-1) were similar to those reported for LDL-apolipoprotein B at steady state during treatment with other HMG-CoA reductase inhibitors. However, after discontinuation of treatment, very low elimination rate constants of 0.09 days-1 for LDL cholesterol and 0.07 days-1 for total apolipoprotein B are obtained. A likely explanation is that the model incorrectly assumes an immediate return to the pretreatment state, whereas transient stimulation of hepatic cholesterol synthesis on discontinuation of therapy with HMG-CoA reductase inhibitors is known to occur.
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Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
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D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000097:blood*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin