Exploration of individuality in drug metabolism by high-throughput metabolomics: The fast line for personalized medicine

Trifonova, Oxana P.; Knight, Richard; Lisitsa, Andrey; Melino, Gerry; Antonov, Alexey V.

doi:10.1016/j.drudis.2015.07.011

Cited by 16 publications

(10 citation statements)

References 40 publications

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“…Metabolomics is a technology used to study and map dynamic changes in organisms before and after stimulation or disturbance, which has been widely applied to research into Chinese medicine because of its feasibility and effectiveness. Combined with pattern recognition analysis, metabolomics can reveal the efficacy and toxicity of Chinese herbs (Trifonova, Knight, Lisitsa, Melino, & Antonov, ; M. Wang et al, ). The combination of urine metabolomics and UPLC–Q‐TOF/MS is a fast, convenient and efficient method for metabolic research.…”

Section: Introductionmentioning

confidence: 99%

Nontargeted urine metabolomics analysis of the protective and therapeutic effects of Citri Reticulatae Chachiensis Pericarpium on high‐fat feed‐induced hyperlipidemia in rats

Zeng

Huang

Luo

et al. 2020

Biomedical Chromatography

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In this study, we focused on studying the changes in urine metabolites in hyperlipidemic rats using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐fight mass spectrometry (UPLC–Q‐TOF/MS) and metabolomics, as well as the effect of Citri Reticulatae Chachiensis Pericarpium (CRCP) on hyperlipidemia. These urine samples were examined by UPLC–Q‐TOF/MS to obtain MS data. The MS data were analyzed by principal component analysis and partial least squares‐discriminant analysis to identify the differential metabolites. CRCP reduced the body weight and levels of triglycerides, total cholesterol and low‐density lipoprotein cholesterol and abnormally decreased high‐density lipoprotein cholesterol in hyperlipidemic rats, which were significantly raised by a high‐fat diet. Twenty‐seven potential biomarkers were identified within the complex sample matrix of urine. Fourteen biomarkers increased in the hyperlipidemia rats compared with normal rats. Meanwhile, 13 biomarkers decreased. CRCP reversed abnormal changes in biomarkers, including 5‐l‐glutamyl‐taurine, 5‐aminopentanoic acid, cis‐4‐octenedioic acid and 2‐octenedioic acid. These biomarkers show that hyperlipidemia is related to the metabolic pathways of taurine and hypotaurine metabolism, fatty acid biosynthesis, and arginine and proline metabolism. CRCP mainly prevents hyperlipidemia by intervening in these metabolic pathways.

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Section: Introductionmentioning

confidence: 99%

Nontargeted urine metabolomics analysis of the protective and therapeutic effects of Citri Reticulatae Chachiensis Pericarpium on high‐fat feed‐induced hyperlipidemia in rats

Zeng

Huang

Luo

et al. 2020

Biomedical Chromatography

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“…So, combined agents with different mechanism of action such as antiresorptive plus anabolic agents or combination of two or more agents with the same mode of action such as inhibitors of bone resorption can be considered as an appropriate strategy for treatment of osteoporosis. However, it should be noticed that the metabolism of a drug is varied individually, and the safety and efficacy of drugs would change according to individual differences [ 92 ]. The combination of BPs and PTH 1-34 or PTH 1-84 in several clinical trials resulted in reduction in anabolic effect of PTH.…”

Section: Introductionmentioning

confidence: 99%

New horizons in treatment of osteoporosis

et al. 2017

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BackgroundPrevalence of osteoporosis is increasing both in developed and developing countries. Due to rapid growth in the burden and cost of osteoporosis, worldwide, it seems reasonable to focus on the reduction of fractures as the main goal of treatment. Although, efficient pharmacological agents are available for the treatment of osteoporosis, there still remains a need to more specific drugs with less adverse effects.Main bodyThis review article provides a brief update on the pathogenesis, presenting current pharmacological products approved by the US Food and Drug Administration (FDA) or Europe, and also newer therapeutic agents to treat osteoporosis according to the clinical trial data available at PubMed, UpToDate, International Osteoporosis Foundation (IOF), and clinical practice guidelines. As well, the effect of combination therapy and recommendations for future research will be further discussed.Short conclusionThe use of current antiresorptive and anabolic agents alone or in combinations for the treatment of osteoporosis entails several limitations. Mainly, their efficacy on non-vertebral fracture reduction is lower than that observed on vertebral fracture. In addition, they have potential adverse events on long time usage. Development of newer agents such as cathepsin k inhibitor and strontium ranelate not only have increased the available options for treating osteoporosis, but also have opened doors of opportunity to improvements in the effective treatment. However, the high cost of new agents have restricted their usage in selective patients who are at high risk of fracture or whom failed response to first line treatment options. Thus, personalized medicine should be considered for future evaluation of genetic risk score and also for environmental exposure assessment. In addition to permanent attention to early diagnosis of osteoporosis and understanding of the pathophysiology of osteoporosis for novel approach in drug discovery, there seems a need to more well-designed clinical trials with larger sample sizes and longer duration on current as well as on newer agents. Also, continuous research on plant-derived components as the source of discovering new agents, and conducting more clinical trials with combination of two or more synthetic drugs, plants, or drug-plant for the treatment of osteoporosis are recommended.Graphical AbstractSummary of treatment modalities for osteoporosis.

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“…Age, weight, liver, and kidney function may also affect the pharmacokinetics of the drug. 30 Food intake can prolong the retention time of the drug in the stomach and change the environment of the gastrointestinal tract, for example, the pH value. Increased pH in the gastrointestinal tract affects the solubility of weak electrolytes.…”

Section: Discussionmentioning

confidence: 99%

Effects of Differential Food Patterns on the Pharmacokinetics of Enteric‐Coated Mesalazine Tablets in the Same Cohort of Healthy Chinese Volunteers

Zhang

Wei

et al. 2019

Clinical Pharm in Drug Dev

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This study aimed to simultaneously determine mesalazine (5-ASA) and its major metabolite N-Ac-5-ASA in the plasma and to evaluate the impact of different food patterns on the relative bioavailability and pharmacokinetics of a single oral dose of 5-ASA in healthy subjects. In this single-dose, open-label, 3-period, 3-treatment crossover study, the subjects received a single, oral dose of 500-mg enteric-coated mesalazine tablet together with either a low-fat or a high-fat breakfast or under fasting condition (reference). The pharmacokinetic parameters were determined by noncompartmental methods and analyzed with a linear mixed-effect model. The geometric least squares mean ratio for the area under the plasma concentration-time curve from zero to infinity of N-Ac-5-ASA was 1.05 (90% confidence interval [CI], 0.70-1.58) for high-fat/fasted condition and 1.06 (90%CI, 0.82-1.36) for low-fat/fasted condition. The least squares mean ratio of 5-ASA was 0.86 (90%CI, 0.65-1.14) for high-fat/fasted condition and 0.78 (90%CI, 0.60-1.02) for low-fat/fasted condition. All P values were >.05. The mean maximum plasma concentration and the time to reach the maximum plasma concentration of N-Ac-5-ASA were 2084 ng/mL, 8 hours; 2639 ng/mL, 11 hours, and 2409 ng/mL, 9 hours for fasted, high-fat, and low-fat, respectively. The values of 5-ASA were 1950 ng/mL, 7 hours; 2869 ng/mL, 9 hours; and 2837 ng/mL, 8 hours for fasted, high-fat, and low-fat condition. 5-ASA was well tolerated under all 3 conditions. Food delayed the absorption of 5-ASA, especially a high-fat meal. Therefore, enteric-coated mesalazine tablets should be taken before meals to avoid causing patients slow response and any effect of food on its efficacy. Keywords food effect, mesalazine, N-acetyl-5-aminosalicylic acid, pharmacokineticsMesalazine, also known as 5-ASA, is a potent drug for inflammatory bowel diseases (IBDs) due to its prominent anti-inflammatory effect. 1 Enteric-coated mesalazine tablets may delay the release of formulation, which help reach a higher concentration locally to reduce the adverse reactions. 5-ASA is metabolized to its main derivative N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) by the N-acetyltransferase I enzyme in the intestinal mucosa and the liver, 2 and both compounds are mainly eliminated via feces. Protein binding of the metabolite N-Ac-5-ASA (80%) is higher than that of 5-ASA (40%). At present, 5-ASA is believed to be therapeutically active and therapeutically inert. N-Ac-5-ASA is the major metabolite present in the blood. 3-5 5-ASA also has therapeutic effect on various types of colitis and Crohn disease, 6 especially for patients with colitis and combined seizures, abdominal pain, diarrhea, and blood in the stool. 7-9

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Exploration of individuality in drug metabolism by high-throughput metabolomics: The fast line for personalized medicine

Cited by 16 publications

References 40 publications

Nontargeted urine metabolomics analysis of the protective and therapeutic effects of Citri Reticulatae Chachiensis Pericarpium on high‐fat feed‐induced hyperlipidemia in rats

Nontargeted urine metabolomics analysis of the protective and therapeutic effects of Citri Reticulatae Chachiensis Pericarpium on high‐fat feed‐induced hyperlipidemia in rats

New horizons in treatment of osteoporosis

Effects of Differential Food Patterns on the Pharmacokinetics of Enteric‐Coated Mesalazine Tablets in the Same Cohort of Healthy Chinese Volunteers

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