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Reinhard H.h. Neubert - One of the best experts on this subject based on the ideXlab platform.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
Sandy Naumann - One of the best experts on this subject based on the ideXlab platform.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
David Loebenberg - One of the best experts on this subject based on the ideXlab platform.
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in vitro and in vivo activities of sch 56592 posaconazole a new triazole Antifungal Agent against aspergillus and candida
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Anthony Cacciapuoti, David Loebenberg, Christine Norris, Erik Corcoran, Fred Menzel, Eugene L Moss, Monika Michalski, Kimberly Raynor, Judith Halpern, Cara MendrickAbstract:SCH 56592 (posaconazole), a new triazole Antifungal Agent, was tested in vitro, and its activity was compared to that of itraconazole against 39 Aspergillus strains and to that of fluconazole against 275 Candida and 9 Cryptococcus strains. The SCH 56592 MICs for Aspergillus ranged from 64 microg/ml. SCH 56592 showed excellent activity against Aspergillus fumigatus and Aspergillus flavus in a pulmonary mouse infection model. When administered therapeutically, the 50% protective doses (PD(50)s) of SCH 56592 ranged from 3.6 to 29.9 mg/kg of body weight, while the PD(50)s of SCH 56592 administered prophylactically ranged from 0.9 to 9.0 mg/kg; itraconazole administered prophylactically was ineffective (PD(50)s, >75 mg/kg). SCH 56592 was also very efficacious against fluconazole-susceptible, -susceptible dose-dependent, or -resistant Candida albicans strains in immunocompetent or immunocompromised mouse models of systemic infection. The PD(50)s of SCH 56592 administered therapeutically ranged from 0.04 to 15.6 mg/kg, while the PD(50)s of SCH 56592 administered prophylactically ranged from 1.5 to 19.4 mg/kg. SCH 56592 has excellent potential for therapy against serious Aspergillus or Candida infections.
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pharmacokinetics of sch 56592 a new azole broad spectrum Antifungal Agent in mice rats rabbits dogs and cynomolgus monkeys
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Amin A Nomeir, David Loebenberg, Anthony Cacciapuoti, G H Miller, Pramila Kumari, Mary Jane Hilbert, Samir K Gupta, Roberta S Hare, Chinchung Lin, Mitchell N CayenAbstract: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-β-cyclodextrin (HPβCD) 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 HPβCD solution (range, 52 to ∼100%) than from the MC suspension (range, 14 to 48%) and was higher in mice (∼100% [HPβCD] and 47% [MC]), rats (∼66% [HPβCD] and 48% [MC]), and dogs (72% [HPβCD] and 37% [MC]) than in monkeys (52% [HPβCD] 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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comparison of a new triazole Antifungal Agent schering 56592 with itraconazole and amphotericin b for treatment of histoplasmosis in immunocompetent mice
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Patricia Connolly, Joe Wheat, Carol T Schnizleinbick, Michelle Durkin, Steve Kohler, Melinda Smedema, J Goldberg, Edward J Brizendine, David LoebenbergAbstract:A murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole Antifungal Agent, Schering (SCH) 56592, for treatment of histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth dilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 μg/ml for SCH 56592, 0.5 μg/ml for amphotericin B, and ≤0.019 μg/ml for itraconazole. Survival studies were done on groups of 10 B6C3F1 mice with a lethal inoculum of 105. All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only 44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29. Fungal burden studies done in similar groups of mice with a sublethal inoculum of 104 showed a reduction in CFUs and Histoplasma antigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH 56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B/kg qod, 0.1 mg of SCH 56592/kg/day, or 10 mg of itraconazole/kg/day). Serum drug concentrations were measured 3 and 24 h after the last dose in mice (groups of five to seven mice), each treated for 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75 and 10 mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg/kg/day (2.15 μg/ml at 3 h and 0.35 μg/ml at 24 h); SCH 56592, 1 mg/kg/day (0.54 μg/ml at 3 h and none detected at 24 h); itraconazole, 75 mg/kg/day (22.53 μg/ml at 3 h and none detected at 24 h); itraconazole, 10 mg/kg/day (1.33 μg/ml at 3 h and none detected at 24 h). Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment of histoplasmosis in humans.
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sch 39304 a new Antifungal Agent oral and topical treatment of vaginal and superficial infections
Medical Mycology, 1993Co-Authors: Raulo Parmegiani, David Loebenberg, Anthony Cacciapuoti, B Antonacci, Christine Norris, F Menzel, L Moss, Taisa Yaroshtomaine, R S Hare, G H MillerAbstract:Sch 39304 is a new broad spectrum triazole Antifungal Agent that is active, orally and topically, against superficial Trichopyton mentagrophytes and vaginal Candida albicans infections. Sch 39304 was compared to fluconazole (FLZ) in a T. mentagrophytes infection model in guinea pigs. Following topical administration, Sch 39304 (0·125%, twice daily, 10 days), was 5–8-fold more effective than FLZ, based on culture and lesion score results. Following oral administration, Sch 39304 (2·5 mg kg-1, once daily, 10 days) produced a dramatic reduction in lesion scores and was 20-fold more active than FLZ; however, due to the length of time it takes for the drugs to reach the infected area of the skin and eradicate the infections, most animals remained culture positive with both drugs. Sch 39304 was also compared with FLZ in a vaginal C. albicans infection in hamsters. Following oral administration (4 days), Sch 39304 (1·6 mg kg-1), cured all hamsters and was 4-fold more active than FLZ. In addition, Sch 39304 as a ...
Jeanphilippe Meyer - One of the best experts on this subject based on the ideXlab platform.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
Andreas Kiesow - One of the best experts on this subject based on the ideXlab platform.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
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controlled nail delivery of a novel lipophilic Antifungal Agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
Journal of Controlled Release, 2014Co-Authors: Sandy Naumann, Jeanphilippe Meyer, Andreas Kiesow, Yahya Mrestani, Johannes Wohlrab, Reinhard H.h. NeubertAbstract:Abstract The penetration behavior into human nails and animal hoof membranes of a novel Antifungal Agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.