Pharmacokinetics of Ciclopirox Olamine after Vaginal Application to Rabbits and Patients

Coppi, G; Silingardi, S; Girardello, R.; Aloysio, Domenico De; Manzardo, S

doi:10.1080/1120009x.1993.11755468

Cited by 5 publications

(3 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its use in treating vaginal candidiasis has also been studied, with limited success (9,17,21), and it has shown clinical promise against azole-resistant Candida species, including C. glabrata. It has demonstrated good topical and systemic tolerance in rats and rabbits when vaginal tissue was examined (5,15) and has been studied in settings with a lower pH (9,10). However, in this study, a 4-fold rise in MIC 90 from 0.5 to 2 g/ml with a decrease in pH was seen.…”

Section: Discussionmentioning

confidence: 99%

Effect of pH on In Vitro Susceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

Danby

Boikov

Rautemaa‐Richardson

et al. 2012

Antimicrob Agents Chemother

100

View full text Add to dashboard Cite

The treatment of vulvovaginal candidiasis (VVC) due to Candida glabrata is challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite of in vitro susceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on the in vitro activity of 11 antifungal agents against 40 C. glabrata isolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibility C. albicans strains. In vitro susceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH, C. glabrata isolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC 90 for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7, C. albicans strains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitive C. albicans isolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrent C. glabrata vaginitis, clinicians should recognize the limitations of in vitro susceptibility testing utilizing pH 7.0.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of pH on In Vitro Susceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

Danby

Boikov

Rautemaa‐Richardson

et al. 2012

Antimicrob Agents Chemother

100

View full text Add to dashboard Cite

show abstract

“…CPX has shown an excellent safety profile and has appeared unable to promote resistance development in fungi in 31 years of use [ 24 , 28 , 29 , 30 ]. Oral, intravaginal, and topical administration routes for CPX have been investigated in humans, but its usage is limited as a topical agent due to poor oral or intravaginal bioavailability, gastrointestinal toxicity, and poor water solubility that limits its production as an injectable drug [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria

Cho

Kim

2022

Pharmaceutics

View full text Add to dashboard Cite

Multidrug-resistant (MDR) Gram-negative bacteria are the top-priority pathogens to be eradicated. Drug repurposing (e.g., the use of non-antibiotics to treat bacterial infections) may be helpful to overcome the limitations of current antibiotics. Zidovudine (azidothymidine, AZT), a licensed oral antiviral agent, is a leading repurposed drug against MDR Gram-negative bacterial infections. However, the rapid emergence of bacterial resistance due to long-term exposure, overuse, or misuse limits its application, making it necessary to develop new alternatives. In this study, we investigated the efficacy of ciclopirox (CPX) as an alternative to AZT. The minimum inhibitory concentrations of AZT and CPX against MDR Gram-negative bacteria were determined; CPX appeared more active against β-lactamase-producing Escherichia coli, whereas AZT displayed no selectivity for any antibiotic-resistant strain. Motility assays revealed that β-lactamase-producing Escherichia coli strains were less motile in nature and more strongly affected by CPX than a parental strain. Resistance against CPX was not observed in E. coli even after 25 days of growth, whereas AZT resistance was observed in less than 2 days. Moreover, CPX effectively killed AZT-resistant strains with different resistance mechanisms. Our findings indicate that CPX may be utilized as an alternative or supplement to AZT-based medications to treat opportunistic Gram-negative bacterial infections.

show abstract

“…Despite only being marketed for topical use, in part because of the large quantity of antibiotics on the market at the time of its development, ciclopirox has been assessed for other purposes, including systemically [6–10]. Acute toxicity studies performed in mice and rats revealed LD 50s ranging from 1,700 to > 2,500 mg/kg (oral and subcutaneous), 71–79 mg/kg (intravenous), and 83–172 mg/kg (intraperitoneal).…”

Section: Introductionmentioning

confidence: 99%

Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli

Conley¹,

Carlson-Banning²,

Carter³

et al. 2019

PLoS ONE

View full text Add to dashboard Cite

New antibiotics are needed against antibiotic-resistant gram-negative bacteria. The repurposed antifungal drug, ciclopirox, equally blocks antibiotic-susceptible or multidrug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates, indicating that it is not affected by existing resistance mechanisms. Toward understanding how ciclopirox blocks growth, we screened E. coli mutant strains and found that disruption of genes encoding products involved in galactose salvage, enterobacterial common antigen synthesis, and transport of the iron binding siderophore, enterobactin, lowered the minimum inhibitory concentration of ciclopirox needed to block growth of the mutant compared to the isogenic parent strain. We found that ciclopirox induced enterobactin production and that this effect is strongly affected by the deletion of the galactose salvage genes encoding UDP-galactose 4-epimerase, galE, or galactose-1-phosphate uridylyltransferase, galT. As disruption of ECA synthesis activates the regulation of capsular synthesis (Rcs) phosphorelay, which inhibits bacterial swarming and promotes biofilm development, we test whether ciclopirox prevents activation of the Rcs pathway. Sub-inhibitory concentrations of ciclopirox increased swarming of the E. coli laboratory K12 strain BW25113 but had widely varying effects on swarming or surface motility of clinical isolate E. coli, A. baumannii, and K. pneumoniae. There was no effect of ciclopirox on biofilm production, suggesting it does not target Rcs. Altogether, our data suggest ciclopirox-mediated alteration of lipopolysaccharides stimulates enterobactin production and affects bacterial swarming.

show abstract

Pharmacokinetics of Ciclopirox Olamine after Vaginal Application to Rabbits and Patients

Cited by 5 publications

References 3 publications

Effect of pH on In Vitro Susceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

Effect of pH on In Vitro Susceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

Repurposing of Ciclopirox to Overcome the Limitations of Zidovudine (Azidothymidine) against Multidrug-Resistant Gram-Negative Bacteria

Sugar and iron: Toward understanding the antibacterial effect of ciclopirox in Escherichia coli

Contact Info

Product

Resources

About