ArticleAntimicrobial agents and chemotherapy2000
Pharmacokinetics of SCH 56592, a new azole broad-spectrum antifungal agent, in mice, rats, rabbits, dogs, and cynomolgus monkeys.
Article in Antimicrobial agents and chemotherapy, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 73 citations in OpenAlex.
- Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations.Clinical pharmacokinetics · 2005Trial
- Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults.Antimicrobial agents and chemotherapy · 2003Trial
- Posaconazole-hemp seed oil loaded nanomicelles for invasive fungal disease.Scientific reports · 2024Article
- Advancing posaconazole quantification analysis with a new reverse-phase HPLC method in its bulk and marketed dosage form.F1000Research · 2023Article
- Pharmacodynamics of Posaconazole in Experimental Invasive Pulmonary Aspergillosis: Utility of Serum Galactomannan as a Dynamic Endpoint of Antifungal Efficacy.Antimicrobial agents and chemotherapy · 2021Article
- Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients.Infection · 2017Review
- Hyperlipidemia Alters the Pharmacokinetics of Posaconazole and Vincristine Upon Co-Administration in Rats.Drugs in R&D · 2017Article
- Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits the Hedgehog Signaling Pathway and Progression of Basal Cell Carcinoma.Molecular cancer therapeutics · 2016Article
- Posaconazole: An Update of Its Clinical Use.Pharmacy (Basel, Switzerland) · 2015Review
- High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Posaconazole and Vincristine in Rat Plasma.International journal of analytical chemistry · 2015Article
- 4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency.Journal of medicinal chemistry · 2014Article
- VNI cures acute and chronic experimental Chagas disease.The Journal of infectious diseases · 2013Article
- Ultra-performance liquid chromatography mass spectrometry and sensitive bioassay methods for quantification of posaconazole plasma concentrations after oral dosing.Antimicrobial agents and chemotherapy · 2010Article
- Conazoles.Molecules (Basel, Switzerland) · 2010Review
- Efficacy of posaconazole against three clinical Aspergillus fumigatus isolates with mutations in the cyp51A gene.Antimicrobial agents and chemotherapy · 2010Article
- Efficacy of triazoles in a murine disseminated infection by Candida krusei.Antimicrobial agents and chemotherapy · 2009Article
- Infection of the subcutis of the nose in a cat caused by Mucor species: successful treatment using posaconazole.Journal of feline medicine and surgery · 2008Article
- Establishing in vitro-in vivo correlations for Aspergillus fumigatus: the challenge of azoles versus echinocandins.Antimicrobial agents and chemotherapy · 2008Article
- Interaction between posaconazole and caspofungin in concomitant treatment of mice with systemic Aspergillus infection.Antimicrobial agents and chemotherapy · 2006Article
- Interaction between posaconazole and amphotericin B in concomitant treatment against Candida albicans in vivo.Antimicrobial agents and chemotherapy · 2005Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SCH 56592 is a new broad-spectrum azole antifungal agent that is in phase 3 clinical trials for the treatment of serious systemic fungal infections. The pharmacokinetics of this drug candidate were evaluated following its intravenous (i.v.) or oral (p.o.) administration as a solution in hydroxypropyl-beta-cyclodextrin (HPbetaCD) or oral administration as a suspension in 0.4% methylcellulose (MC) in studies involving mice, rats, rabbits, dogs, and cynomolgus monkeys. SCH 56592 was orally bioavailable in all species. The oral bioavailability was higher with the HPbetaCD solution (range, 52 to approximately 100%) than from the MC suspension (range, 14 to 48%) and was higher in mice ( approximately 100% [HPbetaCD] and 47% [MC]), rats ( approximately 66% [HPbetaCD] and 48% [MC]), and dogs (72% [HPbetaCD] and 37% [MC]) than in monkeys (52% [HPbetaCD] and 14% [MC]). In rabbits, high concentrations in serum suggested good oral bioavailability with the MC suspension. The i.v. terminal-phase half-lives were 7 h in mice and rats, 15 h in dogs, and 23 h in monkeys. In rabbits, the oral half-life was 9 h. In species given increasing oral doses (mice, rats, and dogs), serum drug concentrations were dose related. Food produced a fourfold increase in serum drug concentrations in dogs. Multiple daily doses of 40 mg of SCH 56592/kg of body weight for eight consecutive days to fed dogs resulted in higher concentrations in serum, indicating accumulation upon multiple dosing, with an accumulation index of approximately 2.6. Concentrations above the MICs and minimum fungicidal concentrations for most organisms were observed at 24 h following a single oral dose in MC suspension in all five species studied (20 mg/kg for mice, rats, and rabbits and 10 mg/kg for dogs and monkeys), suggesting that once-daily administration of SCH 56592 in human subjects would be a therapeutically effective dosage regimen.
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