From the FDA Drug Label
Mean plasma elimination half-life of atorvastatin calcium in humans is approximately 14 hours, but the half-life of inhibitory activity for HMG-CoA reductase is 20 to 30 hours due to the contribution of active metabolites. The half-life of atorvastatin is approximately 14 hours. However, the half-life of its inhibitory activity for HMG-CoA reductase is 20 to 30 hours due to the contribution of active metabolites 1.
From the Research
The half-life of atorvastatin is approximately 7 hours. This information is based on the study by 2, which provides the most direct and relevant data on the pharmacokinetics of atorvastatin. The study states that the total plasma clearance of atorvastatin acid is 625 mL/min and the half-life is about 7 hours.
Key Points About Atorvastatin Pharmacokinetics
- Atorvastatin is completely absorbed after oral administration but undergoes extensive first-pass metabolism, resulting in a bioavailability of 14% 2.
- The volume of distribution of atorvastatin acid is 381L, and plasma protein binding exceeds 98% 2.
- Atorvastatin acid is extensively metabolized in both the gut and liver by oxidation, lactonisation, and glucuronidation, with the metabolites being eliminated by biliary secretion and direct secretion from blood to the intestine 2.
- The renal route is of minor importance (<1%) for the elimination of atorvastatin acid 2.
Clinical Implications
The half-life of atorvastatin and its pharmacokinetic profile support once-daily dosing. However, it's essential to consider the broader context of statin therapy, including the role of active metabolites and the timing of dosing in relation to cholesterol synthesis peaks. Despite the specific half-life of the parent compound, the clinical effects of atorvastatin, including its lipid-lowering efficacy, are sustained due to its active metabolites and the drug's mechanism of action on HMG-CoA reductase.
Evidence Quality and Relevance
The evidence provided by 2 is the most relevant and direct source of information on the half-life of atorvastatin. Other studies, such as 3, 4, 5, and 6, offer additional insights into the pharmacokinetics, efficacy, and safety of atorvastatin but do not supersede the direct measurement of half-life provided by 2. Therefore, when considering the half-life of atorvastatin for clinical decision-making, the data from 2 should be prioritized.