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Rate of Low‐Density Lipoprotein Cholesterol and Apolipoprotein B Changes on Initiation and Discontinuation of Atorvastatin Treatment
Author(s) -
Stern Ralph H.,
Abel Robert B.
Publication year - 1997
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1997.tb04305.x
Subject(s) - atorvastatin , discontinuation , apolipoprotein b , cholesterol , lipoprotein , medicine , apolipoprotein c2 , ldl cholesterol , low density lipoprotein , endocrinology , pharmacology , very low density lipoprotein
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.