Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration
碩士 === 國防醫學院 === 藥學研究所 === 95 === In the study, the analytical method of high performance chromatography(HPLC) was established to determine potential neuroprotective agents, N-methyl-D-aspartate(NMDA) antagonist-dextromethorphan(DXM)and dextrorphan(DXO)levels in vitreous, aqueous and retina followin...
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ndltd-TW-095NDMC05510122015-10-13T16:46:05Z http://ndltd.ncl.edu.tw/handle/93041293321820032528 Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration Dextromethorphan及Dextrorphan經玻璃體內注射給藥之眼部藥物動力學 Ching Ting, Huang 黃靖婷 碩士 國防醫學院 藥學研究所 95 In the study, the analytical method of high performance chromatography(HPLC) was established to determine potential neuroprotective agents, N-methyl-D-aspartate(NMDA) antagonist-dextromethorphan(DXM)and dextrorphan(DXO)levels in vitreous, aqueous and retina following intravitreal injection in New Zealand white rabbits. Ocular pharmacokinetics of DXM and DXO were determined to evaluate the distribution of both drugs in ocular tissues. The condition of the established HPLC method for analyzing ocular tissue levels of DXM and DXO was described as followings. Mobile phase consisted of 0.05 M potassium dihydrogenphosphate, acetonitrile and tetrahydrofuran with a ratio of 75: 25: 0.1(v/v). The HPLC system was equipped with a pump, a fluorescence detector and an autosampler, with a 50 μL loop injector. A reverse phase C8 column was used to analyze the sample, the flow rate was set at 1 mL/min and run at room temperature. The detector was set at 227 and 308 nm for excitation and emission, respectively. Internal standard was ethylmorphine (EM). The HPLC retention times of EM, DXO and DXM were 3.9, 5.2 and 14.8 min, respectively. The analytical method had good linearity in a range of 0.01~0.6 μg/mL for both drugs. Rabbits were intravitreally injected with a single dose of 25 μg(2.5 mg/mL, 10μL) either DXO or DXM. At previously set time points, rabbits were sacrificed by intravenous injection of an overdose of sodium pentobarbital, samples of vitreous, aqueous humor and retina were prepared and analyzed by the developed HPLC method. Pharmacokinetic parameters including apparent volume distribution, clearance and AUC were determined. The time courses of DXM and DXO in vitreous showed two phases of decline with the same peak time at 15 min associated with concentrations 21.78±3.35 μg/mL for DXM and 26.16±1.86 μg/mL for DXO. The apparent volume distributions and terminal elimination half-lives of DXM and DXO, determined from vitreous samples were 2.17±0.61 and 0.47±0.15 mL, as well as 1.49±0.21 and 0.58±0.12 hr, respectively. DXM had a significant higher Vd which was widely distributed in ocular-tissues. DXM also had a higher clearance than that of DXO (0.91±0.16 mL/hr vs 0.50±0.06 mL/hr) in vitreous. The AUC0~8 of vitreous and retina were 52.78±6.03 and 15.88±1.23 μg.hr/g for DXO and 30.70±5.18 and 33.37±3.25 μg.hr/g for DXM. These pharmacokinetic parameters suggested both drugs had different distributive characteristics in ocular tissues that might be further investigated. 江樵熹 2007 學位論文 ; thesis 85 zh-TW |
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碩士 === 國防醫學院 === 藥學研究所 === 95 === In the study, the analytical method of high performance chromatography(HPLC) was established to determine potential neuroprotective agents, N-methyl-D-aspartate(NMDA) antagonist-dextromethorphan(DXM)and dextrorphan(DXO)levels in vitreous, aqueous and retina following intravitreal injection in New Zealand white rabbits. Ocular pharmacokinetics of DXM and DXO were determined to evaluate the distribution of both drugs in ocular tissues.
The condition of the established HPLC method for analyzing ocular tissue levels of DXM and DXO was described as followings. Mobile phase consisted of 0.05 M potassium dihydrogenphosphate, acetonitrile and tetrahydrofuran with a ratio of 75: 25: 0.1(v/v). The HPLC system was equipped with a pump, a fluorescence detector and an autosampler, with a 50 μL loop injector. A reverse phase C8 column was used to analyze the sample, the flow rate was set at 1 mL/min and run at room temperature. The detector was set at 227 and 308 nm for excitation and emission, respectively. Internal standard was ethylmorphine (EM). The HPLC retention times of EM, DXO and DXM were 3.9, 5.2 and 14.8 min, respectively. The analytical method had good linearity in a range of 0.01~0.6 μg/mL for both drugs.
Rabbits were intravitreally injected with a single dose of 25 μg(2.5 mg/mL, 10μL) either DXO or DXM. At previously set time points, rabbits were sacrificed by intravenous injection of an overdose of sodium pentobarbital, samples of vitreous, aqueous humor and retina were prepared and analyzed by the developed HPLC method. Pharmacokinetic parameters including apparent volume distribution, clearance and AUC were determined.
The time courses of DXM and DXO in vitreous showed two phases of decline with the same peak time at 15 min associated with concentrations 21.78±3.35 μg/mL for DXM and 26.16±1.86 μg/mL for DXO. The apparent volume distributions and terminal elimination half-lives of DXM and DXO, determined from vitreous samples were 2.17±0.61 and 0.47±0.15 mL, as well as 1.49±0.21 and 0.58±0.12 hr, respectively. DXM had a significant higher Vd which was widely distributed in ocular-tissues. DXM also had a higher clearance than that of DXO (0.91±0.16 mL/hr vs 0.50±0.06 mL/hr) in vitreous. The AUC0~8 of vitreous and retina were 52.78±6.03 and 15.88±1.23 μg.hr/g for DXO and 30.70±5.18 and 33.37±3.25 μg.hr/g for DXM. These pharmacokinetic parameters suggested both drugs had different distributive characteristics in ocular tissues that might be further investigated.
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author2 |
江樵熹 |
author_facet |
江樵熹 Ching Ting, Huang 黃靖婷 |
author |
Ching Ting, Huang 黃靖婷 |
spellingShingle |
Ching Ting, Huang 黃靖婷 Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration |
author_sort |
Ching Ting, Huang |
title |
Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration |
title_short |
Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration |
title_full |
Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration |
title_fullStr |
Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration |
title_full_unstemmed |
Ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration |
title_sort |
ocular pharmacokinetics of dextromethorphan and dextrorphan following intravitreous administration |
publishDate |
2007 |
url |
http://ndltd.ncl.edu.tw/handle/93041293321820032528 |
work_keys_str_mv |
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