Metabolomics in pharmacology - a delve into the novel field of pharmacometabolomics

ABSTRACT

Introduction: Pharmacometabolomics is an emerging science pursuing the application of precision medicine. Combining both genetic and environmental factors, the so-called pharmacometabolomic approach guides patient selection and stratification in clinical trials and optimizes personalized drug dosage, improving efficacy and safety.

Areas covered: This review illustrates the progressive introduction of pharmacometabolomics as an innovative solution for enhancing the discovery of novel drugs and improving research and development (R&D) productivity of the pharmaceutical industry. An extended analysis on published pharmacometabolomics studies both in animal models and humans includes results obtained in several areas such as hepatology, gastroenterology, nephrology, neuropsychiatry, oncology, drug addiction, embryonic cells, neonatology, and microbiomics.

Expert opinion: a tailored, individualized therapy based on the optimization of pharmacokinetics and pharmacodynamics, the improvement of drug efficacy, and the abolition of drug toxicity and adverse drug reactions is a key issue in precision medicine. Genetics alone has become insufficient for deciphring intra- and inter-individual variations in drug-response, since they originate both from genetic and environmental factors, including human microbiota composition. The association between pharmacogenomics and pharmacometabolomics may be considered the new strategy for an in-deep knowledge on changes and alterations in human and microbial metabolic pathways due to the action of a drug.

KEYWORDS:

• Pharmacometabolomics
• pharmacomicrobomics
• metabotype
• enterotype
• drug toxicity
• individualized therapy

Article highlights

• Pharmacometabolomics is an evolving research area pursuing the achievement of tailored therapeutic regimen

• The power of pharmacometabolomics is hugely increased by integrating metabolic data with pharmacogenomics

• Pharmacometabolomics, associated with other ‘omics’ and information technologies, improves the delivery of precision medicine, overcoming failures in target identification for complex, multifactorial noncommunicable diseases

• Metabotype is the metabolic profile of an individual resulting from genetics, environment, and microbioma interplay

• Pharmacometabolomics identifies the metabolic profile of cancer cells and related changes during chemotherapy

• The term enterotype describes different types of microbial community composition across different body sites

• Gut microbiome has a key role in drug response and effectiveness, by altering the bioavailability, activity, and toxicity of therapeutic drugs

• The manipulation of gut microbiota through diet, probiotics, and antibiotics represents a potential therapeutic tool to achieve the desired drug response

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.