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

Abstract

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.

Nail biology and nail science

“…The significance of this is mainly with respect to inclusion of circulating materials into the nail rather than the other way around, although in a study of topical application of sodium pyrithone, Mayer et al . [225] found microscopic amounts in the systemic circulation. Munro and Shuster [226] and Matthieu et al .…”

Experimental tinea unguium model to assess topical antifungal agents using the infected human nail with dermatophyte in vitro

“…The antifungal drugs were BFZ, a typical topical drug for tinea pedis; AMF, a topical drug for tinea unguium; TBF, an oral drug for tinea unguium; and NaPT, which has good nail penetration. 22 When colony area was used as a measure, the BFZtreated group was found to have improved slightly on the 14th day of drug application, the end point of the evaluation. However, the area of the colony was almost the same as that in the control and vehicle-treated groups.…”

“…This result supports those of Mayer et al on the pharmacokinetics of topical application of NaPT to the nails of rhesus monkeys. 22 Therefore, our model is suitable for evaluating the antifungal activity, including the pharmacokinetics, of an agent in nail tissue. Moreover, the topical antifungal drug for tinea unguium selected using this model should be considered for clinical trials.…”

A Stress Factor for Vitality and Nature: The Effect of Sodium Pyrithione on ACTH and CORT Levels in Rats

“…This situation is thought to be responsible for the increase in the 24-hour period. It has been reported that 85-95% of sodium pyrithione exposure in rats is metabolized and excreted in the urine within 4 days at all dosage levels (Mayer et al, 1992). It can be said that this may be the reason why ACTH and corticosterone levels returned to normal within 96 hours.…”