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  1. Article: A Physiological-Based Pharmacokinetic Model For The Broad Spectrum Antimicrobial Zinc Pyrithione: II. Dermal Absorption And Dosimetry In The Rat.

    Diamond, Gary L / Skoulis, Nicholas P / Jeffcoat, A Robert / Nash, J Frank

    Journal of toxicology and environmental health. Part A

    2021  Volume 84, Issue 15, Page(s) 609–631

    Abstract: The broad spectrum antimicrobial/antifungal zinc pyrithione (ZnPT) is used in products ranging from antifouling paint to antidandruff shampoo. The hazard profile of ZnPT was established based upon comprehensive toxicological testing, and products ... ...

    Abstract The broad spectrum antimicrobial/antifungal zinc pyrithione (ZnPT) is used in products ranging from antifouling paint to antidandruff shampoo. The hazard profile of ZnPT was established based upon comprehensive toxicological testing, and products containing this biocide have been safely used for years. The purpose of this study was to create a dermal physiologically based pharmacokinetic (PBPK) model for ZnPT in the rat for improving dose-response analysis of ZnPT-induced toxicity where reversible hindlimb weakness was the endpoint used as the basis for ZnPT risk assessments. Previously, we developed a PBPK model which simulated the kinetics of pyrithione (PT) and its major metabolites 2-(methylsulfonyl)pyridine and S-glucuronide conjugates in blood and tissues of rats following oral ZnPT administration. The dermal model was optimized utilizing
    MeSH term(s) Absorption, Physiological ; Animals ; Anti-Infective Agents/pharmacokinetics ; Dose-Response Relationship, Drug ; Female ; Organometallic Compounds/pharmacokinetics ; Pyridines/pharmacokinetics ; Rats ; Skin/metabolism
    Chemical Substances Anti-Infective Agents ; Organometallic Compounds ; Pyridines ; pyrithione zinc (R953O2RHZ5)
    Language English
    Publishing date 2021-04-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1413345-3
    ISSN 1528-7394 ; 0098-4108 ; 1087-2620
    ISSN 1528-7394 ; 0098-4108 ; 1087-2620
    DOI 10.1080/15287394.2021.1912678
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1268: Show issues Location:
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  2. Article: A physiologically based pharmacokinetic model for the broad-spectrum antimicrobial zinc pyrithione: I. Development and verification.

    Diamond, Gary L / Skoulis, Nicholas P / Jeffcoat, A Robert / Nash, J Frank

    Journal of toxicology and environmental health. Part A

    2017  Volume 80, Issue 2, Page(s) 69–90

    Abstract: The broad-spectrum antimicrobial zinc pyrithione (ZnPT) is used in numerous products ranging from in-can preservative/mildicide in paints to antidandruff shampoo. Although products containing ZnPT have a long history of safe use, regulatory agencies ... ...

    Abstract The broad-spectrum antimicrobial zinc pyrithione (ZnPT) is used in numerous products ranging from in-can preservative/mildicide in paints to antidandruff shampoo. Although products containing ZnPT have a long history of safe use, regulatory agencies routinely set limits of exposure based upon toxicological considerations. The objective of this study was to create a physiologically based pharmacokinetic (PBPK) model for ZnPT in the rat for improving dose-response analysis of ZnPT-induced toxicity, reversible hindlimb weakness, the endpoint that has been used as the basis for ZnPT risk assessments. A rat oral PBPK model was developed that includes compartments for plasma, liver, kidneys, muscle, brain, and rapidly and slowly perfused tissues. Pyrithione metabolism to 2-(methylsulfonyl)pyridine (MSP) and glucuronide conjugates was incorporated into the model. The model was parameterized and optimized based upon data from single-dose intravenous (iv) and oral gavage pharmacokinetic studies of radiolabeled pyrithione ([
    MeSH term(s) Animals ; Anti-Infective Agents/pharmacokinetics ; Dose-Response Relationship, Drug ; Female ; Models, Biological ; Organometallic Compounds/pharmacokinetics ; Pyridines/pharmacokinetics ; Rats
    Chemical Substances Anti-Infective Agents ; Organometallic Compounds ; Pyridines ; pyrithione zinc (R953O2RHZ5)
    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article
    ZDB-ID 1413345-3
    ISSN 1528-7394 ; 0098-4108 ; 1087-2620
    ISSN 1528-7394 ; 0098-4108 ; 1087-2620
    DOI 10.1080/15287394.2016.1245123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book: Percutaneous penetration of formaldehyde

    Jeffcoat, A. Robert

    report on studies conducted July 1981 to July 1983 (RTI-2009-00-01F)

    1984  

    Institution Bioorganic Chemistry Division, Research Triangle Institute (RTI)
    Author's details A. Robert Jeffcoat. Bioorganic Chemistry Division, Research Triangle Institute (RTI)
    Language Undetermined
    Size 59 S., 13 S. Anh
    Document type Book
    Note Die Vorlage enth. insgesamt ... Werke
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  4. Article: Clinical characteristics and pharmacokinetics of purified soy isoflavones: multiple-dose administration to men with prostate neoplasia.

    Fischer, Leslie / Mahoney, Chrysa / Jeffcoat, A Robert / Koch, Matthew A / Thomas, Brian E / Valentine, John L / Stinchcombe, Thomas / Boan, Jarol / Crowell, James A / Zeisel, Steven H

    Nutrition and cancer

    2004  Volume 48, Issue 2, Page(s) 160–170

    Abstract: A phase I clinical trial was conducted to determine the safety, pharmacokinetic parameters, and efficacy of orally administered isoflavones (genistein and daidzein, potential cancer chemotherapeutic agents) over a 3-mo period in men with prostate ... ...

    Abstract A phase I clinical trial was conducted to determine the safety, pharmacokinetic parameters, and efficacy of orally administered isoflavones (genistein and daidzein, potential cancer chemotherapeutic agents) over a 3-mo period in men with prostate neoplasia. Twenty men, ages 40 and above, with stage B, C, or D adenocarcinoma of the prostate were treated with a multiple-dose regimen of a soy isoflavone formulation (delivering approximately 300 or 600 mg/day genistein and half this much daidzein) for 84 days. The delivered dose of isoflavones was more than 10-fold higher than that typically taken by prostate cancer patients. In men with prostate cancer, relatively minor side effects of chronic isoflavone treatment were observed including some estrogenic effects (breast changes, increased frequency of hot flashes). Serum dehydroepiandrosterone was decreased by 31.7% (P = 0.0004) at the end of treatment. Except for those subjects whose prostate-specific antigen (PSA) values were below 0.4 ng/ml, subjects had a history of increasing PSA levels prior to the trial. This increase continued during the trial both while on soy isoflavones and after treatment was discontinued. On average the rate of rise accelerated after soy isoflavones were discontinued, but that difference did not attain statistical significance. Genistein and daidzein were rapidly cleared from plasma and excreted in urine. Pharmacokinetic data for chronic dose administration were similar to single-dose administration for the isoflavones investigated except that we observed slightly longer circulation time for daidzein.
    MeSH term(s) Adenocarcinoma/drug therapy ; Administration, Oral ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Agents, Phytogenic/blood ; Antineoplastic Agents, Phytogenic/pharmacokinetics ; Dose-Response Relationship, Drug ; Genistein/adverse effects ; Genistein/blood ; Genistein/pharmacokinetics ; Half-Life ; Humans ; Isoflavones/adverse effects ; Isoflavones/blood ; Isoflavones/pharmacokinetics ; Male ; Middle Aged ; Phytoestrogens/adverse effects ; Phytoestrogens/blood ; Phytoestrogens/pharmacokinetics ; Prostatic Neoplasms/drug therapy ; Safety ; Glycine max/chemistry ; Treatment Outcome
    Chemical Substances Antineoplastic Agents, Phytogenic ; Isoflavones ; Phytoestrogens ; daidzein (6287WC5J2L) ; Genistein (DH2M523P0H)
    Language English
    Publishing date 2004-06-30
    Publishing country United States
    Document type Clinical Trial ; Clinical Trial, Phase I ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 424433-3
    ISSN 0163-5581
    ISSN 0163-5581
    DOI 10.1207/s15327914nc4802_5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1496: Show issues Location:
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  5. Article: Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women

    Bloedon, LeAnne T / Jeffcoat, A. Robert / Lopaczynski, Wlodek / Schell, Michael J / Black, Tracy M / Dix, Kelly J / Thomas, Brian F / Albright, Craig / Busby, Marjorie G / Crowell, James A / Zeisel, Steven H

    American journal of clinical nutrition. 2002 Nov., v. 76, no. 5

    2002  

    Abstract: Background: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers. Objective: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, ... ...

    Abstract Background: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers. Objective: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, daidzein, and glycitein in postmenopausal women. Design: Twenty-four healthy postmenopausal women ingested a single dose of 1 of 2 purified (from soybeans) isoflavone preparations that delivered a genistein dose of 2, 4, 8, or 16 mg/kg body wt. These doses were higher than those previously administered to human females. Toxicity studies were performed 24 h and 3, 6, 14, and 30 d after isoflavone administration. Kinetic studies were performed during the first 24 h. Results: We observed a 7% decrease in systolic and diastolic blood pressure and a 32% decrease in the neutrophil count 24 h after treatment with formulation A. Isolated episodes of nausea, pedal edema, and breast tenderness were judged to be possibly related to the study treatment. The terminal plasma half-lives for free genistein, daidzein, and glycitein averaged 3.8, 7.7, and 3.4 h, respectively. The terminal pseudo half-lives for total genistein and total daidzein in plasma averaged 10.1 and 10.8 h, respectively. The estimated bioavailabilities of both total genistein and total daidzein from each of the 2 formulations were not significantly different. Conclusions: A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12-24-h intervals would not lead to progressive accumulation of these isoflavones.
    Keywords bioavailability ; daidzein ; diastolic blood pressure ; edema ; females ; genistein ; glycitein ; half life ; nausea ; neoplasms ; pharmacokinetics ; postmenopause ; soybeans ; toxicity ; toxicity testing ; women
    Language English
    Dates of publication 2002-11
    Size p. 1126-1137.
    Document type Article
    ZDB-ID 280048-2
    ISSN 1938-3207 ; 0002-9165
    ISSN (online) 1938-3207
    ISSN 0002-9165
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  6. Article: Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women.

    Bloedon, LeAnne T / Jeffcoat, A Robert / Lopaczynski, Wlodek / Schell, Michael J / Black, Tracy M / Dix, Kelly J / Thomas, Brian F / Albright, Craig / Busby, Marjorie G / Crowell, James A / Zeisel, Steven H

    The American journal of clinical nutrition

    2002  Volume 76, Issue 5, Page(s) 1126–1137

    Abstract: Background: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers.: Objective: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, ...

    Abstract Background: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers.
    Objective: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, daidzein, and glycitein in postmenopausal women.
    Design: Twenty-four healthy postmenopausal women ingested a single dose of 1 of 2 purified (from soybeans) isoflavone preparations that delivered a genistein dose of 2, 4, 8, or 16 mg/kg body wt. These doses were higher than those previously administered to human females. Toxicity studies were performed 24 h and 3, 6, 14, and 30 d after isoflavone administration. Kinetic studies were performed during the first 24 h.
    Results: We observed a 7% decrease in systolic and diastolic blood pressure and a 32% decrease in the neutrophil count 24 h after treatment with formulation A. Isolated episodes of nausea, pedal edema, and breast tenderness were judged to be possibly related to the study treatment. The terminal plasma half-lives for free genistein, daidzein, and glycitein averaged 3.8, 7.7, and 3.4 h, respectively. The terminal pseudo half-lives for total genistein and total daidzein in plasma averaged 10.1 and 10.8 h, respectively. The estimated bioavailabilities of both total genistein and total daidzein from each of the 2 formulations were not significantly different.
    Conclusions: A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12-24-h intervals would not lead to progressive accumulation of these isoflavones.
    MeSH term(s) Aged ; Blood Pressure/drug effects ; Dose-Response Relationship, Drug ; Drug Combinations ; Female ; Genistein/blood ; Genistein/urine ; Half-Life ; Humans ; Isoflavones/administration & dosage ; Isoflavones/adverse effects ; Isoflavones/blood ; Isoflavones/pharmacokinetics ; Isoflavones/pharmacology ; Isoflavones/urine ; Middle Aged ; Postmenopause/drug effects ; Postmenopause/metabolism ; Glycine max/chemistry
    Chemical Substances Drug Combinations ; Isoflavones ; daidzein (6287WC5J2L) ; glycitein (92M5F28TVF) ; Genistein (DH2M523P0H)
    Language English
    Publishing date 2002-09-28
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 280048-2
    ISSN 1938-3207 ; 0002-9165
    ISSN (online) 1938-3207
    ISSN 0002-9165
    DOI 10.1093/ajcn/76.5.1126
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Clinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy men.

    Busby, Marjorie G / Jeffcoat, A Robert / Bloedon, LeAnne T / Koch, Matthew A / Black, Tracy / Dix, Kelly J / Heizer, William D / Thomas, Brian F / Hill, Judith M / Crowell, James A / Zeisel, Steven H

    The American journal of clinical nutrition

    2001  Volume 75, Issue 1, Page(s) 126–136

    Abstract: Background: Soy isoflavones are potential cancer chemoprevention treatments.: Objective: We conducted safety studies of purified unconjugated genistein, daidzein, and glycitein, and defined pharmacokinetic parameters for their absorption and ... ...

    Abstract Background: Soy isoflavones are potential cancer chemoprevention treatments.
    Objective: We conducted safety studies of purified unconjugated genistein, daidzein, and glycitein, and defined pharmacokinetic parameters for their absorption and metabolism.
    Design: Thirty healthy men ingested a single dose of 1 of 2 isoflavone preparations purified from soy. The delivered doses of genistein (1, 2, 4, 8, or 16 mg/kg body wt) were higher than those previously administered to humans. Formulation A was composed of 90 +/- 5% genistein, 10% daidzein, and 1% glycitein. Formulation B was composed of 43% genistein, 21% daidzein, and 2% glycitein.
    Results: We observed no clinically significant behavioral or physical changes after treatment. We observed elevations in lipoprotein lipase and hypophosphatemia that were possibly related to the treatment but that were associated with no clinical toxicity. Considerable quantities of isoflavones were excreted in urine as conjugates. The terminal elimination rate, elimination half-life, area under the curve, maximum plasma concentration, apparent systemic clearance, and volume of distribution were estimated for genistein and daidzein. The mean elimination half-lives with both formulations were 3.2 h for free genistein and 4.2 h for free daidzein. The mean pseudo half-lives were 9.2 h for total genistein and 8.2 h for total daidzein.
    Conclusions: Dietary supplements of purified unconjugated isoflavones administered to humans in single doses exceeding normal dietary intake manyfold resulted in minimal clinical toxicity. Genistein and daidzein (free and total) were rapidly cleared from plasma and excreted in urine.
    MeSH term(s) Adult ; Anticarcinogenic Agents/blood ; Anticarcinogenic Agents/pharmacokinetics ; Estrogens, Non-Steroidal/blood ; Estrogens, Non-Steroidal/pharmacokinetics ; Genistein/blood ; Genistein/pharmacokinetics ; Half-Life ; Humans ; Isoflavones/adverse effects ; Isoflavones/blood ; Isoflavones/pharmacokinetics ; Male ; Glycine max
    Chemical Substances Anticarcinogenic Agents ; Estrogens, Non-Steroidal ; Isoflavones ; daidzein (6287WC5J2L) ; glycitein (92M5F28TVF) ; Genistein (DH2M523P0H)
    Language English
    Publishing date 2001-12-18
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 280048-2
    ISSN 1938-3207 ; 0002-9165
    ISSN (online) 1938-3207
    ISSN 0002-9165
    DOI 10.1093/ajcn/75.1.126
    Database MEDical Literature Analysis and Retrieval System OnLINE

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