PD
What do Pravastatin and Rosuvastatin's primary role?
It mainly works in your liver to lower "bad" cholesterol (LDL) and triglycerides, while slightly raising “good” cholesterol (HDL). As it produces less cholesterol, it makes more LDL receptors. These receptors clear LDL from the blood, lowering circulating LDL-C.This helps keep your blood vessels clearer and healthier.
How much of Pravastatin and Rosuvastatin get absorbed, and what is the Tmax?
The bioavailability of pravastatin is 17% whereas rosuvastatin is 20%. Tmax for pravastatin is 1-1.5hrs and rosuvastatin is 3-5 hrs
Do genetics affect how pravastatin works? How?
Yes, one important factor for pravastatin is the variation in the SLCO1B1 gene, which encodes the hepatic transporter, OATP1B1, a protein that transports pravastatin.
What is the main similarity between rosuvastatin and pravastatin
both pravastatin and rosuvastatin are statins, they lower cholesterol by inhibiting HMG-CoA reductase in the liver.
This is the primary enzyme in the liver that statins (rosuvastatin and pravstatin) block to reduce cholesterol
HMG-CoA reductase
How do both drugs differ in protein binding and Volume of distribution?
Pravastatin around 50% protein bound; rosuvastatin around 90% bound. The Vd of pravastatin is 0.5L/kg, rosuvastatin is 134L/kg
How do genetics affect pravastatin's pharmacology?
Pravastatin relies on OATP1B1 to enter the liver, where it blocks HMG-CoA reductase, reducing cholesterol synthesis. Individuals carrying reduced-function SLCO1B1 variants have impaired transporter activity. This decreases hepatic uptake of pravastatin, leading to lower concentrations at its site of action but higher plasma levels.
What is the main difference between the two drugs?
The main difference is that pravastatin is less potent and cleared mainly unchanged by the kidneys, while rosuvastatin is more potent and its clearance involves both the liver (via transporters) and the kidneys, making rosuvastatin effective at lower doses.
How does pravstatin and rosuvastatin protect the heart?
By lowering bad cholesterol, it reduces the risk of heart attacks, strokes, and clogged arteries. It also decreases the risk of atherosclerosis and cardiovascular disease
What enzymes metabolise these drugs and drug-drug interactions?
Pravastatin undergoes metabolism mainly through non-cyp pathways (sulfation, hydroxylation), whereas rosuvastatin around 20% metabolism primarily through CYP2C9. Pravastatin has fewer drug-drug interactions ; rosuvastatin has low but some cyp-mediated risk
What are the consequences if a patient has this gene variant?
Reduced efficacy: less pravastatin reaches the liver, so cholesterol-lowering may be weaker.
Increased risk of toxicity: as elevated systemic concentrations increase the likelihood of statin-associated side effects, particularly myopathy.
Which statin is more hydrophilic, and what does that mean for side effects?
Pravastatin is more hydrophilic than rosuvastatin, meaning it stays mostly in the liver and less in muscle and other tissues, so it generally carries a lower risk of muscle-related side effects compared with more lipophilic statins.
Pradastatin also reduces the livers production of VLDL. What is this and what is the effect?
The early form of LDL, so both LDL and trygliceride levels fall. At the same time it can raise HDL which carries cholesterol back to the liver in a process called reverse cholesterol
What are the main routes of elimination for pravastatin and rosuvastatin?
Pravastatin: ~20% renal unchanged, majority biliary/fecal. Rosuvastatin: ~90% feces unchanged, ~10% urine.
True or False: data showing females homozygous for reduced function allele, SLCO1B1*5, had higher rates of raised cholesterol (48.4% vs 41.7%) and more frequent statin medication discontinuation (29.5% vs 25.7%).
True
Which drug has a higher percentage of first rate metabolsim?
pravastatin
How does the potency of Rosuvastatin affect its ability to lower cholsterol?
Rosuvastatin is stronger because it lowers LDL more effectively and sometimes faster than other statins e.g pravastatin
How do their half-lives differ, and what does this mean for clinical uses?
Pravastatin half-life is 1-1.5hr, which means less time spent in the body. ROsuvastatin’s half-life is 19hrs, which means it spends a longer time in the body and is very potent.
What is the difference in the pharmacogenetics between the two drugs?
Both pravastatin and rosuvastatin are influenced by SLCO1B1 variants, but pravastatin is more dependent on OATP1B1 protein, making it especially sensitive to reduced-function alleles. Rosuvastatin is affected by SLCO1B1 as well, but its pharmacogenetics are broader, with ABCG2 variants playing a major role in altering drug exposure. Clinically, pravastatin pharmacogenetics are linked mainly to efficacy and side-effect risk, while rosuvastatin has official guidance recommending dose adjustment in known carriers of high-exposure genotypes.
Does rosuvastatin undergo sulfation?
No, pravastatin undergoes sulfation and hydroxylation. Rosuvastatin metabolises through a CYP enzyme.