What is the difference between fat-soluble and water-soluble statins? What are the differences when using them?

A friend left a message to Huazi, asking him, "I heard that there is a difference between fat solubility and water solubility among statins. Does this difference have any effect on the efficacy?" Huazi said that the main structure of all statins is similar, but the properties of the substituents attached to the main structure are different, which leads to differences in fat solubility and water solubility among different statins.

The difference between statins in terms of "fat solubility" and "water solubility" will affect the distribution of the drugs in the human body, but will have little effect on the efficacy. The main difference is in the side effects of the drugs.

1. The difference between drug lipid solubility and water solubility Human cholesterol is mainly synthesized in liver cells, and statins mainly enter liver cells to exert their effects. The cell membranes of the human body are composed of lipids, so liver cell membranes are more easily penetrated by drugs with high lipid solubility. In other words, statins with high lipid solubility are more likely to enter liver cells to exert their effects. However, high lipid solubility also means that it is easy to enter other cells and has low selectivity for the liver.

Water-soluble statins are not easy to penetrate the liver cell membrane. They mainly rely on the special transporter proteins on the liver cell membrane to actively absorb them and enter the liver cells to exert their effects. Relatively speaking, water-soluble statins are more selective for the liver.

2. Fat-soluble statins and water-soluble statins Among statins, simvastatin, lovastatin, and pitavastatin are fat-soluble statins. Fluvastatin and atorvastatin are water- and lipid-soluble statins; pravastatin and rosuvastatin are water-soluble statins.

If they are ranked by fat solubility, they are simvastatin > lovastatin > pitavastatin > fluvastatin > atorvastatin > rosuvastatin > pravastatin.

In addition to being easy to enter liver cells, statins with high fat solubility can also easily penetrate the blood-brain barrier and enter the central nervous system, affecting the central nervous system and easily causing side effects such as dizziness, headache, and memory loss. Statins with high fat solubility can also easily enter muscle cells, causing side effects such as muscle fatigue and soreness.

Relatively speaking, statins with strong water solubility only work in liver cells, and have less impact on the central nervous system and muscles. However, the occurrence of side effects is also closely related to the lipid-lowering strength of statins themselves. For example, although rosuvastatin is a water-soluble statin, it is also a potent statin. According to research statistics, the incidence of muscle damage caused by it is higher than that of atorvastatin, which is also a potent statin.

Statins with strong fat solubility have a greater impact on liver function, but it is also related to the properties of the drug itself. For example, pitavastatin is a fat-soluble statin, but it is not metabolized in the liver, so its impact on liver function is smaller.

3. "Fat-soluble" or "water-soluble" is not the only criterion for measuring side effects. Although fat-soluble statins are more likely to enter the liver and affect liver function, water-soluble statins also "work in" liver cells, so they will also affect liver function. Therefore, whether using "fat-soluble" or "water-soluble" statins, liver function is an indicator that needs attention, and the drug needs to be discontinued after the transaminase (AST, ALT) increases by more than 3 times.

In the same way, all statins may cause muscle damage, and creatine kinase (CK) should be monitored during medication. If it exceeds 5 times the normal upper limit, the drug should be discontinued. All statins have no adverse effects on renal function, but when renal function is impaired, it will affect the excretion of water-soluble statins, and attention should be paid to dose adjustment, but the metabolism of fat-soluble statins is not affected.

To sum up, the fat solubility and water solubility of statins will affect the distribution of drugs in the body, but have little effect on the efficacy, mainly in terms of side effects. But this effect is not the only one, it is also affected by many factors such as dosage, efficacy, and individual differences in drug sensitivity. Therefore, when taking the medicine, it is necessary to follow the doctor's guidance and monitor adverse reactions. I am pharmacist Huazi, welcome to follow me and share more health knowledge.