Zinc pyridinethione: Serum metabolites of zinc pyridinethione in rabbits, rats, monkeys, and dogs after oral dosing

Gibson, Wade

doi:10.1016/0041-008x(82)90122-3

Cited by 26 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, there are numerous studies evaluating systemic exposure to salt/chelates of pyrithione in animal models that are used in the human dermal risk assessment of this material [5-14]. These studies have shown route specific differences in dose-adverse effects following oral or intravenous administration [7, 10, 15-17] compared to topically administered ZnPT from shampoos [7] or aqueous formulations, when oral ingestion was prevented [11]. Such outcomes reflect the ability of ZnPT to persist on the surface of the skin, i.e.…”

Section: Introductionmentioning

confidence: 99%

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

Rush

Nash

Smith

et al. 2019

Skin Pharmacol Physiol

View full text Add to dashboard Cite

Background: Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT. Objectives: To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[¹⁴C]PT was investigated. Method: In vitro penetration of [¹⁴C]PT into and through excised human skin was measured following application of Zn[¹⁴C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum. Results: The steady-state flux and cumulative absorption of Zn[¹⁴C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[¹⁴C]PT and ³H₂O absorption when dosed from both aqueous formulations, but not from castor oil. Conclusion: These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [¹⁴C]PT kinetics, is controlled by particle dissolution and molecular speciation.

show abstract

Section: Introductionmentioning

confidence: 99%

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

Rush

Nash

Smith

et al. 2019

Skin Pharmacol Physiol

View full text Add to dashboard Cite

show abstract

“…Only 1-2% of a so dium 35S-pyrithione solution was absorbed across rhesus monkey skin following a single dose [10].…”

Section: Discussionmentioning

confidence: 99%

Topical and Systemic Absorption of Sodium Pyrithione following Topical Application to the Nails of the Rhesus Monkey

Mayer

Couch²,

Erickson³

et al. 1992

Skin Pharmacol Physiol

View full text Add to dashboard Cite

A study was performed to investigate the local penetration into the nail, the systemic absorption into the rest of the body, and the routes of excretion of sodium pyrithione following topical application to the nail. Approximately 20 µ1 of a film-forming 3% sodium ¹⁴C-pyrithione solution was applied once daily to 5 fingernails and 5 toenails of 4 rhesus monkeys for 6 or 7 days. Following dose removal on study day 7, 2 animals were sacrificed, and the treated nails were analyzed for radioactivity. The other 2 monkeys received the topical dose for 1 more day and were monitored during the postdosing period. Sodium ¹⁴C-pyrithione was absorbed slowly into and across the nail following topical application, with the nails serving as reservoirs for the drug. Further evidence of the slow movement of sodium pyrithione across the nail was provided by peak plasma ¹⁴C equivalents obtained on day 9, 1 day after the last dose had been removed from the nails. Only slight drug concentrations were measurable in plasma, with no radioactivity observed beyond day 12. The urinary excretion data exhibited a delay in peak urinary excretion (days 8 and 9), and an elimination half-life of 2 days, so that approximately 90% of the absorbed drug was eliminated within 1 week following treatment. Including a minor excretion pathway through the feces, total excretion as a percent of dosage was 8.5 %, indicating that less than 10% of the applied topical dose of sodium pyrithione was absorbed systemically. Because monkey and human nails have similar absorptive characteristics, it is likely that corresponding levels of sodium pyrithione equivalents would be absorbed across human nails treated with sodium pyrithione.

show abstract

“…It has also been administered to laboratory animals for toxicity testing and to probe the effects of zinc homeostasis in vivo . In these tests, the complex demonstrated high potency (Jeffcoat et al, 1980; Gibson et al, 1982; Jasim and Tjalve, 1986a,b). However, the compound lacks solubility in water and is poorly bioavailable (Jasim and Tjalve, 1986b).…”

Section: Rationale For Developing New Zinc Ionophoresmentioning

confidence: 99%

Texaphyrins and water-soluble zinc(II) ionophores: development, mechanism of anticancer activity, and synergistic effects

Preihs¹,

Magda

Sessler³

2013

BioInorganic Reaction Mechanisms

View full text Add to dashboard Cite

Texaphyrins, first prepared by Sessler and coworkers in the 1980s, represent early examples of expanded porphyrins. This class of pentaaza, oligopyrrolic macrocycles demonstrates excellent tumor localization and metal-chelating properties. In biological milieus, texaphyrins act as redox mediators and are able to produce reactive oxygen species. Furthermore, texaphyrins have been shown to upregulate zinc in vivo, an important feature that inspired us to develop new zinc ionophores that might allow the same function to be elicited but via a simpler chemical means. In this review, the basic properties of texaphyrins and the zinc ionophores they helped spawn will be discussed in the cadre of developing an understanding that could lead to the preparation of new, redox-active anticancer agents.

show abstract

Zinc pyridinethione: Serum metabolites of zinc pyridinethione in rabbits, rats, monkeys, and dogs after oral dosing

Cited by 26 publications

References 33 publications

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin

Topical and Systemic Absorption of Sodium Pyrithione following Topical Application to the Nails of the Rhesus Monkey

Texaphyrins and water-soluble zinc(II) ionophores: development, mechanism of anticancer activity, and synergistic effects

Contact Info

Product

Resources

About