The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies

Zarezadeh, Meysam; Saedisomeolia, Ahmad; Shekarabi, Mahoor; Khorshidi, Masoud; Emami, Mohammad Reza; Müller, Daniel J.

doi:10.1007/s00394-020-02421-y

Cited by 42 publications

(33 citation statements)

References 111 publications

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“…As reported, smoking and nutrition are associated with the activity variation of CYPs [ 77 , 78 ]. It was shown that smokers had higher CYP2D6, CYP2E1, and CYP2B6 levels compared with nonsmokers [ 69 , 79 ].…”

Section: Individual Variation Of Cyp-mediated Drug Metabolismmentioning

confidence: 99%

Cytochrome P450 Enzymes and Drug Metabolism in Humans

Zhao

Ma²,

et al. 2021

IJMS

438

147

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Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1–3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.

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Section: Individual Variation Of Cyp-mediated Drug Metabolismmentioning

confidence: 99%

Cytochrome P450 Enzymes and Drug Metabolism in Humans

Zhao

Ma²,

et al. 2021

IJMS

438

147

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“…In 2020, Zarezadeh et al reviewed the available studies examining the effects of human obesity on CYP drug metabolizing activities (135). Most of the studies indicated a decrease in CYP1A2 and CYP3A4/5.…”

Section: Studies Involving Rodentsmentioning

confidence: 99%

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

et al. 2022

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In many comparative trials examining the effects of adult obesity on pharmacokinetics of drugs, conclusions were made based on values that were either not adjusted to total body weight or adjusted to non-obese body mass (e.g., ideal or lean body weight). In many cases these values were higher in the obese subjects. We have reviewed the data from comparative human trials, and it is apparent that in examining clearance normalization to total body weight (as typically done in studies involving pediatric obese patients), the clearances are often reduced in the obese. We have also reviewed the results of experimental obese versus non-obese rodent models. Those studies have mostly found that the systemic exposures to the same dose per body weight are increased, with obesity-related decreases in clearance. Furthermore, the expression of a number of important drug metabolizing enzymes are reduced in the experimental obese state. There is also evidence that obesity causes increases in the measured mass of eliminating organs such as liver and kidney. Human clearance normalized to total body weight appears to better reflect the underlying changes reported in the expression of protein and functional activity of drug clearance mechanisms.

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“…Drug distribution and bioavailability cannot be directly predicted by body changes in obese individuals but strongly depend on the physicochemical properties of the respective drugs [ 18 ]. In the last 50 years or so, there have been a lot of clinical trials on CYP-mediated drug metabolism in obese and normal weight individuals, as well as effects of dietary compositions on the pharmacokinetics of different drug classes [ 7 ].…”

Section: Dietmentioning

confidence: 99%

“…As alluded to previously, several studies show that the activity of the CYP system can be strongly altered by the composition of a meal in terms of protein, carbohydrate and fat content (summarized in [ 7 ]). The different macronutrients affected CYP450 enzymes differentially but the findings were not always conclusive.…”

Section: Dietmentioning

confidence: 99%

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The Impact of Diet and Exercise on Drug Responses

Niederberger

Parnham

2021

IJMS

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It is well known that lifestyle changes can alter several physiological functions in the human body. For exercise and diet, these effects are used sensibly in basic therapies, as in cardiovascular diseases. However, the physiological changes induced by exercise and a modified diet also have the capacity to influence the efficacy and toxicity of several drugs, mainly by affecting different pharmacokinetic mechanisms. This pharmacological plasticity is not clinically relevant in all cases but might play an important role in altering the effects of very common drugs, particularly drugs with a narrow therapeutic window. Therefore, with this review, we provide insights into possible food–drug and exercise–drug interactions to sharpen awareness of the potential occurrence of such effects.

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The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies

Cited by 42 publications

References 111 publications

Cytochrome P450 Enzymes and Drug Metabolism in Humans

Cytochrome P450 Enzymes and Drug Metabolism in Humans

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

The Impact of Diet and Exercise on Drug Responses

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