Preclinical pharmacokinetics of fosciclopirox, a novel treatment of urothelial cancers, in rats and dogs

Basit Öğe Kaydı
dc.contributor.authorWeir, Scott J.
dc.contributor.authorWood, Robyn
dc.contributor.authorSchorno, Karl
dc.contributor.authorBrinker, Amanda E.
dc.contributor.authorRamamoorthy, Prabhu
dc.contributor.authorHeppert, Kathy
dc.contributor.authorTaylor, John A., III
dc.contributor.authorTanol, Mehmet
dc.date.accessioned2021-05-15T12:42:27Z
dc.date.available2021-05-15T12:42:27Z
dc.date.issued2019
dc.departmentEczacılık Fakültesien_US
dc.descriptionBrinker, Amanda/0000-0003-1134-0572; Weir, Scott/0000-0002-8020-434X
dc.description.abstractPharmacokinetic studies in rats and dogs were performed to characterize the in vivo performance of a novel prodrug, fosciclopirox. Ciclopirox olamine (CPX-O) is a marketed topical antifungal agent with demonstrated in vitro and in vivo preclinical anticancer activity in several solid tumor and hematologic malignancies. The oral route of administration for CPX-O is not feasible due to low bioavailability and dose-limiting gastrointestinal toxicities. To enable parenteral administration, the phosphoryl-oxymethyl ester of ciclopirox (CPX), fosciclopirox (CPX-POM), was synthesized and formulated as an injectable drug product. In rats and dogs, intravenous CPX-POM is rapidly and completely metabolized to its active metabolite, CPX. The bioavailability of the active metabolite is complete following CPX-POM administration. CPX and its inactive metabolite, ciclopirox glucuronide (CPX-G), are excreted in urine, resulting in delivery of drug to the entire urinary tract. The absolute bioavailability of CPX following subcutaneous administration of CPX-POM is excellent in rats and dogs, demonstrating the feasibility of this route of administration. These studies confirmed the oral bioavailability of CPX-O is quite low in rats and dogs compared with intravenous CPX-POM. Given its broad-spectrum anticancer activity in several solid tumor and hematologic cancers and renal elimination, CPX-POM is being developed for the treatment of urothelial cancer. The safety, dose tolerance, pharmacokinetics, and pharmacodynamics of intravenous CPX-POM are currently being characterized in a United States multicenter first-in-human Phase 1 clinical trial in patients with advanced solid tumors.en_US
dc.description.sponsorshipNational Institutes of Health National Cancer Institute Cancer Center Support Grant [P30 CA168524]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA168524, R01CA190291] Funding Source: NIH RePORTERen_US
dc.description.sponsorshipResearch reported in this presentation was supported by the National Institutes of Health National Cancer Institute Cancer Center Support Grant [Grant P30 CA168524] and by a public-private partnership between The Institute for Advancing Medical Innovation at the University of Kansas Medical Center and CicloMed LLC, Kansas City, MO.en_US
dc.identifier.doi10.1124/jpet.119.257972
dc.identifier.endpage159en_US
dc.identifier.issn0022-3565
dc.identifier.issn1521-0103
dc.identifier.issue2en_US
dc.identifier.pmid31113837
dc.identifier.scopus2-s2.0-85069296748
dc.identifier.scopusqualityQ2
dc.identifier.startpage148en_US
dc.identifier.urihttps://doi.org/10.1124/jpet.119.257972
dc.identifier.urihttps://hdl.handle.net/20.500.12939/938
dc.identifier.volume370en_US
dc.identifier.wosWOS:000477702600002
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorTanol, Mehmet
dc.language.isoen
dc.publisherAmer Soc Pharmacology Experimental Therapeuticsen_US
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectFosciclopiroxen_US
dc.subjectCiclopiroxen_US
dc.subjectCiclopirox Glucuronideen_US
dc.subjectPharmacokineticsen_US
dc.subjectDrug Metabolismen_US
dc.subjectExcretionen_US
dc.subjectBladder Canceren_US
dc.subjectAllometric Scalingen_US
dc.titlePreclinical pharmacokinetics of fosciclopirox, a novel treatment of urothelial cancers, in rats and dogs
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
tanol.pdf
Boyut:
702.73 KB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin/ Full Text
İndir

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
Eczacılık Fakültesi Yayın Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu