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  1. Article ; Online: Composite CYP3A phenotypes influence tacrolimus dose-adjusted concentration in lung transplant recipients.

    Liu, Michelle / Shaver, Ciara M / Birdwell, Kelly A / Heeney, Stephanie A / Shaffer, Christian M / Van Driest, Sara L

    Pharmacogenetics and genomics

    2022  Volume 32, Issue 5, Page(s) 209–217

    Abstract: Objectives: Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A4/5 isoenzymes (encoded by CYP3A4 and CYP3A5). Guidelines for adjusting tacrolimus based on CYP3A5 test results are published; however, ...

    Abstract Objectives: Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A4/5 isoenzymes (encoded by CYP3A4 and CYP3A5). Guidelines for adjusting tacrolimus based on CYP3A5 test results are published; however, CYP3A4 variants also contribute to the variability in tacrolimus pharmacokinetics. The effects of composite phenotypes incorporating CYP3A5 and CYP3A4 increased (*1G, *1B) and decreased (*22) function variants have not been evaluated. The objective of this study is to investigate the impact of both increased and decreased function CYP3A variants on weight and dose-adjusted tacrolimus concentration (C0/D).
    Methods: We performed a single-center retrospective cohort study of lung transplant recipients to evaluate the median tacrolimus C0/D by composite CYP3A phenotype groups during the index transplant hospitalization. CYP3A4 and CYP3A5 alleles were used to classify patients into four CYP3A groups from least to most CYP3A activity. Exploratory analyses of ABCB1 and additional candidate genes were also assessed.
    Results: Of the 92 included individuals, most (58) were CYP3A Group 2. The median tacrolimus C0/D differed significantly between CYP3A groups (P = 0.0001). CYP3A Group 2 median tacrolimus C0/D was 190.5 (interquartile range: 147.6-267.5) (ng/ml)/(mg/kg/d) and significantly higher than Group 4 [107.9 (90.4-116.1), P = 0.0001)]. Group 2 median tacrolimus C0/D did not significantly differ from Group 1 and Group 3 [373.5 (149.2-490.3) and 81.4 (62.6-184.1), respectively]. No significant differences in tacrolimus C0/D were found for the ABCB1 diplotypes.
    Conclusion: These data indicate that a composite CYP3A phenotype incorporating both increase and decrease variant information from CYP3A4 in addition to CYP3A5 may significantly influence tacrolimus C0/D during the early postoperative period.
    MeSH term(s) Cytochrome P-450 CYP3A/genetics ; Cytochrome P-450 CYP3A/metabolism ; Genotype ; Humans ; Immunosuppressive Agents/pharmacokinetics ; Kidney Transplantation ; Lung ; Phenotype ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Tacrolimus/pharmacokinetics ; Transplant Recipients
    Chemical Substances Immunosuppressive Agents ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Tacrolimus (WM0HAQ4WNM)
    Language English
    Publishing date 2022-04-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2175826-8
    ISSN 1744-6880 ; 0960-314X ; 1744-6872
    ISSN (online) 1744-6880
    ISSN 0960-314X ; 1744-6872
    DOI 10.1097/FPC.0000000000000472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3660: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Safety and tolerability of high-intensity statin therapy in heart transplant patients receiving immunosuppression with tacrolimus.

    Heeney, Stephanie A / Tjugum, Shelby L / Corkish, Morgan E / Hollis, Ian B

    Clinical transplantation

    2018  Volume 33, Issue 1, Page(s) e13454

    Abstract: Background: Following heart transplantation (HT), HMG CoA reductase inhibitors (statins) have been shown to reduce total and low-density lipoprotein (LDL) cholesterol, development of cardiac allograft vasculopathy (CAV), and mortality. Studies in HT ... ...

    Abstract Background: Following heart transplantation (HT), HMG CoA reductase inhibitors (statins) have been shown to reduce total and low-density lipoprotein (LDL) cholesterol, development of cardiac allograft vasculopathy (CAV), and mortality. Studies in HT patients have demonstrated the safety of low/moderate intensity statins; however, little data exist using high-intensity (HI) statins. The study aim was to evaluate the safety and efficacy of HI statins in HT recipients receiving tacrolimus.
    Methods: This single-center, retrospective analysis included adult HT recipients from January 1, 2005, to December 31, 2015, who received HI statin therapy during posttransplant follow-up. The primary outcome, tolerability, was defined as the absence of myalgias, hepatotoxicity, rhabdomyolysis, or HI statin dose reduction/discontinuation. The secondary end point was the mean reduction in total and LDL cholesterol.
    Results: Among the 24 patients included, one experienced myalgias and therapy discontinuation (4%; P > 0.99). No other HI statin dose reduction/discontinuation occurred, and no instances of rhabdomyolysis or hepatotoxicity were observed. The average reduction in total and LDL cholesterol after conversion to HI statin was 35 mg/dL (P = 0.02) and 19 mg/dL (P = 0.10), respectively.
    Conclusions: High-intensity statin therapy appears safe and efficacious in HT recipients receiving tacrolimus and is a reasonable option for the treatment of refractory hyperlipidemia.
    MeSH term(s) Adult ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Heart Diseases/surgery ; Heart Transplantation/methods ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hyperlipidemias/prevention & control ; Immunosuppressive Agents/therapeutic use ; Incidence ; Male ; Maximum Tolerated Dose ; Middle Aged ; Postoperative Complications/drug therapy ; Postoperative Complications/epidemiology ; Prognosis ; Retrospective Studies ; Tacrolimus/therapeutic use ; United States/epidemiology
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Immunosuppressive Agents ; Tacrolimus (WM0HAQ4WNM)
    Language English
    Publishing date 2018-12-18
    Publishing country Denmark
    Document type Clinical Trial ; Journal Article
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.13454
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2204: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Evaluation of the Safety of Intravenous Thiamine Administration in a Large Academic Medical Center.

    Tjugum, Shelby L / Hedrick, Tanner L / Jean, Stephanie J / Heeney, Stephanie A / Rohde, Kalynn A / Campbell-Bright, Stacy L

    Journal of pharmacy practice

    2019  Volume 34, Issue 3, Page(s) 397–402

    Abstract: Background/objective: Previous literature describes increased incidence of infusion-related reactions when administering thiamine doses greater than 100 mg as an intravenous (IV) push. The purpose of this evaluation was to assess the safety of ... ...

    Abstract Background/objective: Previous literature describes increased incidence of infusion-related reactions when administering thiamine doses greater than 100 mg as an intravenous (IV) push. The purpose of this evaluation was to assess the safety of administering higher doses of thiamine as IV push compared to infusion.
    Methods: A single-center, retrospective review was performed from June to October 2017. Included patients were aged 18 years or older and received 1 dose of IV thiamine 200 mg or greater. Patients were divided into 2 groups: group 1 included patients who received 200-mg IV push and, group 2 included patients who received any dose greater than 200 mg. The primary objective was to quantify and compare rate of adverse reactions between the 2 groups. Institutional thiamine prescribing practices were examined. Wilcoxon Rank Sum and Fischer exact tests were performed.
    Results: Sixty-six percent of patients were male, and the median age was 55 years (interquartile range [IQR]: 44-63). Fifty percent received 200-mg IV push, 20% received a combination of IV infusion and IV push, and 30% received IV infusion. Adverse reactions possibly due to thiamine administration occurred in 4 (2.0%) patients. One patient received 200 mg via IV infusion, while 3 received 200 mg via IV push. There was no significant difference in adverse reaction rate between IV push and IV infusion administrations (
    Conclusion: Our results support administering thiamine doses of 200 mg or less as an IV push. Given lack of robust safety data, it is recommended to continue to dilute doses greater than 200 mg and infuse over 30 minutes.
    MeSH term(s) Academic Medical Centers ; Administration, Intravenous ; Adolescent ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Retrospective Studies ; Thiamine/adverse effects
    Chemical Substances Thiamine (X66NSO3N35)
    Language English
    Publishing date 2019-09-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1027474-1
    ISSN 1531-1937 ; 0897-1900
    ISSN (online) 1531-1937
    ISSN 0897-1900
    DOI 10.1177/0897190019872584
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2893: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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