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      Poly‐pharmacokinetic Study of a Multicomponent Herbal Medicine in Healthy Chinese Volunteers

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          Abstract

          The advent of mass spectrometry-based analytical technologies coupled with multivariate statistical methods offer tremendous new opportunities for understanding the pharmacokinetics (PKs) of multicomponent herbal medicines (HMs). We recently proposed a poly-PK strategy to characterize the concentration-time profile and the metabolic response profile of multicomponent HMs using an integrated phytochemical and metabolomics approach. Here, we provided the first example of the poly-PK strategy, in which we simultaneously characterized the PK as well as the metabolic response profiles of a Chinese HM, Huangqi decoction (HQD, consisting of Radix Astragali and Radix Glycyrrhizae), in healthy Chinese volunteers. Using the poly-PK approach, we identified 56 HQD-derived compounds and 292 biotransformed HQD metabolites in human plasma. Additionally, we acquired the concentration-time profiles of these plasma HQD metabolites and correlated them with a plasma metabolomics profile consisting of 166 human endogenous metabolites that were significantly altered in response to HQD intervention.

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          Sex differences in pharmacokinetics and pharmacodynamics.

          Offie Soldin, Donald R Mattison (2009)
          Significant differences that exist between the sexes affect the prevalence, incidence and severity of a broad range of diseases and conditions. Men and women also differ in their response to drug treatment. It is therefore essential to understand these reactions in order to appropriately conduct risk assessment and to design safe and effective treatments. Even from that modest perspective, how and when we use drugs can result in unwanted and unexpected outcomes. This review summarizes the sex-based differences that impact on pharmacokinetics, and includes a general comparison of clinical pharmacology as it applies to men, women and pregnant women. Sex-related or pregnancy-induced changes in drug absorption, distribution, metabolism and elimination, when significant, may guide changes in dosage regimen or therapeutic monitoring to increase its effectiveness or reduce potential toxicity. Given those parameters, and our knowledge of sex differences, we can derive essentially all factors necessary for therapeutic optimization. Since this is a rapidly evolving area, it is essential for the practitioner to review drug prescribing information and recent literature in order to fully understand the impact of these differences on clinical therapeutics.
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            The footprints of gut microbial-mammalian co-metabolism.

            Xiaojiao Zheng, Guoxiang Xie, Aihua Zhao … (2011)
            Gut microbiota are associated with essential various biological functions in humans through a "network" of microbial-host co-metabolism to process nutrients and drugs and modulate the activities of multiple pathways in organ systems that are linked to different diseases. The microbiome impacts strongly on the metabolic phenotypes of the host, and hence, metabolic readouts can give insights into functional metagenomic activity. We applied an untargeted mass spectrometry (MS) based metabonomics approach to profile normal Wistar rats exposed to a broad spectrum β-lactam antibiotic imipenem/cilastatin sodium, at 50 mg/kg/daily for 4 days followed by a 14-day recovery period. In-depth metabolic phenotyping allowed identification of a panel of 202 urinary and 223 fecal metabolites significantly related to end points of a functional metagenome (p < 0.05 in at least one day), many of which have not been previously reported such as oligopeptides and carbohydrates. This study shows extensive gut microbiota modulation of host systemic metabolism involving short-chain fatty acids, tryptophan, tyrosine metabolism, and possibly a compensatory mechanism of indole-melatonin production. Given the integral nature of the mammalian genome and metagenome, this panel of metabolites will provide a new platform for potential therapeutic markers and mechanistic solutions to complex problems commonly encountered in pathology, toxicology, or drug metabolism studies.
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              Herbal medicines and perioperative care.

              J. Moss, C Yuan, Jessica Lee (2001)
              Widespread use of herbal medications among the presurgical population may have a negative impact on perioperative patient care. To review the literature on commonly used herbal medications in the context of the perioperative period and provide rational strategies for managing their preoperative use. The MEDLINE and Cochrane Collaboration databases were searched for articles published between January 1966 and December 2000 using the search terms herbal medicine, phytotherapy, and alternative medicine and the names of the 16 most commonly used herbal medications. Additional data sources were obtained from manual searches of recent journal articles and textbooks. We selected studies, case reports, and reviews addressing the safety and pharmacology of 8 commonly used herbal medications for which safety information pertinent to the perioperative period was available. We extracted safety, pharmacodynamic, and pharmacokinetic information from the selected literature and reached consensus about any discrepancies. Echinacea, ephedra, garlic, ginkgo, ginseng, kava, St John's wort, and valerian are commonly used herbal medications that may pose a concern during the perioperative period. Complications can arise from these herbs' direct and pharmacodynamic or pharmacokinetic effects. Direct effects include bleeding from garlic, ginkgo, and ginseng; cardiovascular instability from ephedra; and hypoglycemia from ginseng. Pharmacodynamic herb-drug interactions include potentiation of the sedative effect of anesthetics by kava and valerian. Pharmacokinetic herb-drug interactions include increased metabolism of many drugs used in the perioperative period by St John's wort. During the preoperative evaluation, physicians should explicitly elicit and document a history of herbal medication use. Physicians should be familiar with the potential perioperative effects of the commonly used herbal medications to prevent, recognize, and treat potentially serious problems associated with their use and discontinuation.
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                Author and article information

                Journal
                Title: Clinical Pharmacology & Therapeutics
                Abbreviated Title: Clin. Pharmacol. Ther.
                Publisher: Wiley
                ISSN (Print): 0009-9236
                ISSN (Electronic): 1532-6535
                Publication date Created: September 25 2017
                Publication date Created: April 2018
                Publication date (Electronic): September 19 2017
                Publication date (Print): April 2018
                Volume: 103
                Issue: 4
                Pages: 692-702
                Affiliations
                [1 ]Center for Translational MedicineShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai China
                [2 ]University of Hawaii Cancer CenterHonolulu Hawaii USA
                [3 ]E‐Institute of Shanghai Municipal Education CommitteeShanghai University of Traditional Chinese MedicineShanghai China
                [4 ]Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai China
                [5 ]Department of Pharmacology, School of PharmacyShanghai University of Traditional Chinese MedicineShanghai China
                [6 ]Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of PharmacySichuan UniversityChengdu China
                [7 ]State Key Laboratory of Drug Delivery Technology and PharmacokineticsTianjin Institute of Pharmaceutical ResearchTianjin China
                Article
                DOI: 10.1002/cpt.784
                PubMed ID: 28675423
                SO-VID: cb57f3a3-f4e2-403d-9f04-59db29d99f1b
                Copyright © © 2018
                License:

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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