Spin-echo 1H n.m.r. spectroscopy: a new method for studying penicillin metabolism

Journal of Pharmacy and Pharmacology

Jennings

Woodnutt

1985

19F NMR spectroscopy was used to monitor the metabolites of flucloxacillin in the urine of a rat dosed with its sodium salt. 19F NMR signals were detected and quantified from flucloxacillin and three metabolites. The 19F NMR method involves minimal sample preparation and is free from interference by endogenous urine components. High-field spin-echo 1H NMR spectroscopy and HPLC were used to confirm the results.

mentioning

confidence: 99%

“…It has recently been shown by Everett et al (1984) that high-field, spin-echo 1H NMR spectroscopy is R useful method for studying the metabolites of penicillins in urine, with some advantages over conventional methods. IH NMR spectroscopy has also been used recently (Bales et all984) to study the urinary metabolites of paracetamol (acetaminophen).…”

mentioning

confidence: 99%

19F NMR spectroscopy study of the metabolites of flucloxacillin in rat urine

Journal of Pharmacy and Pharmacology

Jennings

Woodnutt

1985

“…The use of these approaches increased significantly in the 1980s with the advent of advanced pulsed Fourier transform nuclear magnetic resonance (NMR) spectroscopy (Lindon et al, 1999) and hyphenated mass spectrometry (MS) (Theodoridis et al, 2011) analytical technologies capable of profiling dozens to hundreds of metabolites in biological fluids such as urine or blood plasma. Early applications were established in the investigation of drug metabolism (Everett et al, 1984), toxicology (Holmes et al, 1992), inborn errors of metabolism (Iles et al, 1985) and the understanding of disease states (Bales et al, 1984). Metabolic profiling is now termed metabonomics or metabolomics (Lindon et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

2016

Front. Pharmacol.

Self Cite

Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalized medicine, that is the selection of medicines for subgroups of patients so as to maximize drug efficacy and minimize toxicity, is a key goal of twenty-first century healthcare. Currently, most personalized medicine paradigms rely on clinical judgment based on the patient's history, and on the analysis of the patients' genome to predict drug effects i.e., pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as “the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures.” The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments.

“…NMR spectroscopy has been an important tool for the study of metabolite profiles in biological fluids since the early 1980s. 21 The applications of the technology are manifold and include the direct study of drug metabolism for relatively high-dosage drugs, 22 the study of drug safety, and the study of disease states, 23 all of prime importance for drug discovery and development.…”

Section: Metabolic Profiling Metabonomics and Pharmacometabonomicsmentioning

confidence: 99%

Drug Discovery and Development: the Role of NMR

2015

eMagRes

Self Cite

NMR spectroscopy has been a technology of fundamental importance to drug discovery and development for the past 40-50 years, principally through its use in the structure elucidation of leads, drugs, their synthetic intermediates, and the degradation products and impurities of those drug molecules. In the past 30 years, another major area of application of NMR spectroscopy has been metabolic profiling or metabonomics studies of drug metabolism, drug safety, drug efficacy, and disease, through studies of biological fluids such as urine and plasma, representing a change in application from the chemical to the biological sciences. This trend has continued with significant progress in the application of in vivo MRI and magnetic resonance spectroscopy (MRS) to the study of disease states and their treatment in patients and in animal models. More recently, new applications of NMR spectroscopy have emerged such as hit-finding and hit-to-lead optimization, impacting directly on these early stages of the drug discovery process. Finally, the discovery of completely new areas, led by NMR spectroscopy, such as pharmacometabonomics, holds out the promise of improvements in personalized medicine in the future. This article will briefly cover all of these areas, and more, as a prelude to more detailed treatments in the following articles of this work.