What is the pharmacokinetics of atorvastatin?
Atorvastatin presents a dose-dependent and non-linear pharmacokinetic profile. It is very rapidly absorbed after oral administration. After the administration of a dose of 40 mg, its peak plasma concentration of 28 ng/ml is reached 1-2 hours after initial administration with an AUC of about 200 ng∙h/ml.
What is the pharmacodynamics of atorvastatin?
Mechanism of Action Atorvastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. [2] By preventing the conversion of HMG-CoA to mevalonate, statin medications decrease cholesterol production in the liver.
What is the bioavailability of atorvastatin?
Oral bioavailability of atorvastatin calcium (ATC) is very low (only 14%) due to instability and incomplete intestinal absorption and/or extensive gut wall extraction.
What are the metabolites of atorvastatin?
Liver metabolism produces two active hydroxy metabolites, ortho‐hydroxy‐atorvastatin (o‐OH‐atorvastatin) and para‐hydroxy‐atorvastatin (p‐OH‐atorvastatin), and three corresponding inactive lactone metabolites [11]. The active metabolites are equipotent to the parent drug in vitro.
How long does atorvastatin stay in your system?
by Drugs.com It takes about 77 hours (3 days) for atorvastatin to be out of your system. The elimination half life of atorvastatin is approximately 14 hours. This is the time it takes for your body to reduce plasma drug levels by half.
What are the common side effects of atorvastatin?
Common Lipitor side effects are diarrhea, upset stomach, muscle and joint pain, and changes in some blood tests, according to Pfizer Inc….Common Side Effects of Lipitor
- Cold-like symptoms.
- Joint pain.
- Diarrhea.
- Urinary tract infection.
- Stomach pain.
- Nausea.
- Muscle pain and spasms.
- Difficulty falling and staying asleep.
What is the side effects of atorvastatin?
Side effects of Lipitor (atorvastatin) include:
- Cold-like symptoms.
- Joint pain.
- Diarrhea.
- Urinary tract infection.
- Stomach pain.
- Nausea.
- Muscle pain and spasms.
- Difficulty falling and staying asleep.
What is the contraindications of atorvastatin?
Atorvastatin is contraindicated in patients with active hepatic disease (including cholestasis, hepatic encephalopathy, hepatitis, and jaundice) or unexplained persistent elevations in serum aminotransferase concentrations.
Why statins are given at bedtime?
Many statins work more effectively when they are taken at night. This is because the enzyme which makes the cholesterol is more active at night. Also, the half-life, or the amount of time it takes for half the dose to leave your body, of some statins is short.
How is atorvastatin absorbed?
Atorvastatin acid is highly soluble and permeable, and the drug is completely absorbed after oral administration. However, atorvastatin acid is subject to extensive first-pass metabolism in the gut wall as well as in the liver, as oral bioavailability is 14%.
Is atorvastatin metabolized in the liver?
Atorvastatin is largely metabolized in the liver via CYP 3A4 and excreted in bile. The mild, self-limited ALT elevations are likely due to a toxic intermediate of drug metabolism and the reversal of these elevations due to adaptation.
How are statins metabolized?
Most of the statins are metabolized through the cytochrome P450 (CYP) metabolic pathway; atorvastatin (Lipitor), simvastatin (Zocor), and lovastatin (Mevacor, Altocor) via the CYP3A4 isoenzyme, and fluvastatin (Lescol) via CYP2C9.
Why is lactone a strong inhibitor of atorvastatin?
Because atorvastatin lactone has a significantly higher metabolic clearance and the lactone is a strong inhibitor of atorvastatin acid metabolism, it can be expected that metabolism of the lactone is the relevant pathway for atorvastatin elimination and drug interactions.
How many ether glucuronides does atorvastatin lactone produce?
Atorvastatin lactone yields a single ether glucuronide (G3). G3 formation best fit Michaelis-Menten kinetics (K (m) = 2.6 microM, V (max) = 10.6 pmol/min/mg).
Do statins undergo glucuronidation and lactonization in the human liver?
Of the statins studied, SVA underwent glucuronidation and lactonization in human liver microsomes, with the lowest CL(int) (0.4 microl/min/mg of protein for SVA versus approximately 3 microl/min/mg of protein for AVA and CVA).
How can lactone compounds in serum be stabilized?
The lactone compounds in serum could be stabilized by lowering the working temperature to 4 degrees C or lowering the serum pH to 6.0.