The effectiveness of painkillers is really different when you take them while standing, lying down, or sitting!

When we experience physical discomfort or pain, every minute we wait for painkillers to take effect is not only a physical torture, but also a mental torture. For a long time, we can only "bear it" and "endure it" and wait for the drugs to take effect. Recently, research has found that we may try to speed up the effect of drugs and relieve pain faster by assuming a specific posture, that is, lying on the right side.

Can these gestures on the packaging speed up the effect of the drug? Image from the Internet

Where is the drug absorbed

Since 1918, scientists have noticed that when subjects lie on their right side after taking a barium meal (an oral contrast medium used to diagnose the digestive tract), their stomachs empty faster. This discovery has inspired continued research into the postural effect in the hope of uncovering the physiological mechanisms behind it.

Have you ever thought about how to take medicine to get the fastest effect? ​​Image from pixabay.com

Before we discuss how posture affects drug efficacy, we need to understand the absorption process of oral drugs in the body. After we take the drugs, they reach the stomach through the esophagus, are dispersed, dissolved and diluted by the digestive juices, and then enter the small intestine. This transfer process from the stomach to the duodenum is called gastric emptying.

For most drugs, the extent of gastric absorption is negligible. The main area of ​​drug absorption is the upper small intestine, especially the duodenum, because it has a wide absorption surface and sufficient blood supply. In the small intestine, drug molecules pass through the intestinal wall, enter the blood circulation, and finally reach the target tissue or organ through the blood to exert their effects.

There are many factors that affect drug absorption in the gastrointestinal tract, including drug dissolution and release rate, gastrointestinal environment, intestinal absorption surface area, gastrointestinal secretion and motility, local blood flow and diet.

To study how posture and body position affect the onset of drug effect is to understand how these direct factors change under different postures.

A three-dimensional stomach model used to study how posture affects drug efficacy. Source: Reference [3]

How does posture affect how well a drug works?

The gastric emptying process is an important rate-limiting step in the early stages of oral drug absorption. Taking the common antipyretic drug acetaminophen as an example, the average time for half of the drug to be absorbed in the small intestine is about 6.8 minutes, while the average time for half of the stomach to be emptied is about 12 minutes. Based on this, scientists began to study how body position affects the time that liquids and solids stay in the stomach.

A study conducted by Anvari M et al. from McMaster University in Canada found that lying on the right side can speed up gastric emptying compared with sitting and standing, while lying on the left side and lying on the back usually lead to slower mixing, dilution and gastric emptying.

GolubAL and others from Kaifu Pharmaceuticals in the United States believe that this phenomenon is caused by changes in the size and liquid distribution of the stomach in different postures. Generally speaking, the larger the volume of the stomach, the faster it empties, and the stomach volume is the largest when lying on the right side. In addition, when lying on the right side, the pylorus connecting the stomach and the duodenum is in a lower position, and gravity can accelerate gastric emptying. When lying on the left side or in the supine position, the pylorus is facing upward, and gravity cannot accelerate the gastric emptying process.

The geometric shape of the stomach in different postures (A) upright (B) prone (C) right side (D) supine (E) left side Source: Reference [2]

Changes in body position also affect the flow and distribution of blood in our bodies. When we change from lying to sitting or standing, the blood will accumulate in the lower part of the body due to the effect of gravity, causing the plasma in the blood vessels to flow into the gaps between organs and tissue cells, and the indicators such as hemoglobin, red blood cells, white blood cells and platelets in the blood will increase significantly.

Abalan et al. (Abalan F) from the Bordeaux Specialist Medical Center in France found that this plasma loss will lead to corresponding changes in drug concentrations in the blood, especially for drugs that are more bound to proteins (such as insulin, heparin, antibody drugs, etc.). Therefore, the absorption rate of some protein drugs may be slower when sitting and standing. In addition, some studies have pointed out that the blood flow to the liver and kidneys will also change in different body positions. Compared with the supine position, the blood flow to the liver is reduced by 37% in the upright position, which may significantly affect the absorption and metabolism of oral drugs.

Researchers at the Hebrew University of Jerusalem found that posture also affects the autonomic nervous system, which indirectly affects absorption. When lying on the right side, the tension of the vagus nerve increases, while when lying on the left side, the tension of the sympathetic nerve increases. The tension of the vagus nerve and the sympathetic nerve affects gastrointestinal motility, which may be one of the reasons why lying on the right side absorbs faster than lying on the left side.

How effective can posture and body position really be?

It can be seen that the absorption of oral drugs is affected by multiple systems of the human body and is affected by many complex factors. Therefore, the current in vitro experimental methods used to evaluate the absorption effect of oral drugs still face significant limitations when studying this field.

To overcome these limitations, Professor Rajat Mittal of Johns Hopkins University in the United States took an innovative approach, using computer simulation to quantitatively analyze the specific effects of body posture on drug absorption. The research team constructed a mathematical model that comprehensively considers the physicochemical properties of the drug, the flow characteristics of the fluid in the stomach, and the kinetic process of drug dissolution. Using this model, the researchers were able to simulate and predict the behavior of drugs in the stomach when affected by different postures.

Scientists use models to simulate gastric peristalsis. Image source: Reference [3]

The results of the study show that human posture has a significant effect on the dissolution and absorption process of drugs. Compared with supine and left-side decubitus positions, upright, prone and right-side decubitus positions can make oral medications show their efficacy more quickly. Taking ibuprofen as an example, the right-side decubitus position is the fastest position for it to take effect, which only takes about 10 minutes; the upright position takes about 23 minutes; and the left-side decubitus position takes about 100 minutes to take effect. Of course, these simulation results are for reference only, and are also related to the meals and contents when taking the medicine. The actual effect will vary due to individual differences.

Conclusion

Although these studies may not be directly relevant to most people, they are of particular significance to certain populations, such as those with gastric diseases, bedridden patients or the elderly. These populations may face problems such as gastroparesis, delayed gastric emptying or body posture restrictions, which may further affect the dissolution and absorption of drugs in the gastrointestinal tract. Understanding how posture affects drug absorption can help improve drug absorption efficiency and treatment effects in these populations, and relieve their pain or other symptoms, which has great clinical significance. References

[1] Queckenberg, Christian, and Uwe Fuhr. "Influence of postureonpharmacokinetics." Europeanjournalofclinicalpharmacology 65(2009):109-119.

[2] Imai, Yohsuke, etal. "Antralrecirculationinthestomachduringgastricmixing." AmericanJournalofPhysiology-GastrointestinalandLiverPhysiology 304.5(2013):G536-G542.

[3] Lee, Jae H., et al. "Computational modeling of drug dissolution in the human stomach: Effects of posture and gastroparesison drug bioavailability." Physics of Fluids 34.8 (2022).

[4] Seo, JungHee, and Rajat Mittal. "Computational modeling of drug dissolution in the human stomach." Frontiers in Physiology 12 (2022): 755997.

[5] Palmada, Nadun, et al. "ASystematicReviewofComputationalFluidDynamicsModelsintheStomachandSmallIntestine." AppliedSciences 13.10(2023):6092.

Author: Denovo Science Team

Review丨Liu Guiyang, Chief Pharmacist, Fourth Medical Center, PLA General Hospital