The Experts below are selected from a list of 6966 Experts worldwide ranked by ideXlab platform
Edward H. Kerns - One of the best experts on this subject based on the ideXlab platform.
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Profiling impurities and degradants of Butorphanol tartrate using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry substructural techniques
Journal of Pharmaceutical and Biomedical Analysis, 1996Co-Authors: Kevin J. Volk, Robyn A. Rourick, Steven E. Klohr, Edward H. KernsAbstract:Abstract A rapid and systemic strategy based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural techniques was utilized to elucidate the degradation products of Butorphanol, the active ingredient in stadol® NS. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray mass spectrometry, and tandem mass spectrometry to rapidly and accurately elucidate structues of impurities and degradants. In these studies, several low-level degradation products were observed in long-term storage stability samples of bulk Butorphanol. The resulting analytical profile includes information on five degradants including molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. The degradation products formed during long-term storage of Butorphanol tartrate included oxidative products proposed as 9-hydroxy- and 9-keto-Butorphanol, norButorphanol, a ring-contraction degradant, and Δ1, 10α-Butorphanol. These methodologies are applicable at any stage of the drug product cycle from discovery through to development. This library of Butorphanol degradants provides a foundation for future development work regarding product monitoring, as well as a useful diagnosite tool for new degradation products.
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profiling impurities and degradants of Butorphanol tartrate using liquid chromatography mass spectrometry and liquid chromatography tandem mass spectrometry substructural techniques
Journal of Pharmaceutical and Biomedical Analysis, 1996Co-Authors: Kevin J. Volk, Robyn A. Rourick, Steven E. Klohr, Edward H. KernsAbstract:Abstract A rapid and systemic strategy based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural techniques was utilized to elucidate the degradation products of Butorphanol, the active ingredient in stadol® NS. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray mass spectrometry, and tandem mass spectrometry to rapidly and accurately elucidate structues of impurities and degradants. In these studies, several low-level degradation products were observed in long-term storage stability samples of bulk Butorphanol. The resulting analytical profile includes information on five degradants including molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. The degradation products formed during long-term storage of Butorphanol tartrate included oxidative products proposed as 9-hydroxy- and 9-keto-Butorphanol, norButorphanol, a ring-contraction degradant, and Δ1, 10α-Butorphanol. These methodologies are applicable at any stage of the drug product cycle from discovery through to development. This library of Butorphanol degradants provides a foundation for future development work regarding product monitoring, as well as a useful diagnosite tool for new degradation products.
Rashmi H. Barbhaiya - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetic Interaction Between Butorphanol Nasal Spray and Oral Metoclopramide in Healthy Women
Journal of clinical pharmacology, 1997Co-Authors: Nimish N. Vachharajani, Wen Chyi Shyu, Rashmi H. BarbhaiyaAbstract:The pharmacokinetics of Butorphanol nasal spray, with and without the coadministration of metoclopramide, were studied in 24 healthy women. In this crossover study all volunteers received 3 treatments: a single, 1-mg dose of Butorphanol nasal spray, a single, 10-mg oral dose of metoclopramide, and a combination of a single, 1-mg dose of Butorphanol nasal spray and a single, 10-mg oral dose of metoclopramide. There was at least a one-week washout period between sessions. Serial blood samples were collected and plasma samples analyzed using a validated radioimmunoassay to determine the concentration of Butorphanol, or a high-performance liquid chromatography/ultraviolet procedure was used to determine the concentration of metoclopramide. There were no statistically significant differences in the pharmacokinetic parameters, Cmax, tmax, AUC, and t1/2, for Butorphanol with or without metoclopramide. Similarly, except for a delay in tmax of metoclopramide with coadministration of Butorphanol, the pharmacokinetic parameters of metoclopramide were not significantly different between two treatments. Thus, the pharmacokinetics of both Butorphanol and metoclopramide were not significantly altered when administered in combination. The incidence of nausea/vomiting after Butorphanol administration was substantially reduced by coadministration of metoclopramide. Based on the pharmacokinetic and safety results, it can be concluded that Butorphanol nasal spray and metoclopramide can be administered in combination without altering the dose regimen of either drug.
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Lack of pharmacokinetic interaction between Butorphanol tartrate nasal spray and sumatriptan succinate.
The Journal of Clinical Pharmacology, 1995Co-Authors: Nuggehally R. Srinivas, Wen Chyi Shyu, David H. Upmalis, Rashmi H. BarbhaiyaAbstract:The pharmacokinetics of Butorphanol tartrate given in a nasal spray with and without the co-administration of sumatriptan succinate were studied in 24 healthy men and women. In this crossover design study, all subjects received 2 treatments: a single 1-mg dose of Butorphanol nasal spray and a 1-mg dose of Butorphanol nasal spray plus a single 6-mg subcutaneous (SC) dose of sumatriptan. There was a two-week washout period between sessions. Serial blood samples were collected and plasma samples analyzed using validated radioimmunoassay and high-performance liquid chromatography/electrochemical procedures to determine the concentrations of unchanged Butorphanol and sumatriptan, respectively. There were no statistically significant differences for Butorphanol between the 2 treatments on any of the following pharmacokinetic parameters: Cmax, tmax, AUC, t1/2, CL/f, and Vz/f. Similarly, the pharmacokinetic parameters obtained for sumatriptan (given with Butorphanol nasal spray) were comparable with the literature values obtained for a single 6-mg SC dose of sumatriptan. These data show a lack of pharmacokinetic interaction between Butorphanol nasal spray and sumatriptan. Butorphanol nasal spray and sumatriptan were well tolerated. The adverse experience profiles of Butorphanol nasal spray were comparable between the treatments, with and without sumatriptan. It can be concluded that regimens of Butorphanol nasal spray and sumatriptan need not be changed for either pharmacokinetic or safety considerations when the two compounds are co-administered in treating acute migraine attacks.
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Multiple‐dose phase I study of transnasal Butorphanol
Clinical pharmacology and therapeutics, 1993Co-Authors: Wen Chyi Shyu, Kenneth A. Pittman, Donald S. Robinson, Rashmi H. BarbhaiyaAbstract:The safety, tolerance, and pharmacokinetics of transnasal Butorphanol were evaluated in a double-blind, multiple-dose phase I study. A total of 18 subjects received either placebo (n= 6) or a single transnasal dose of 2 mg Butorphanol tartrate on the first day and 1, 2, and 4 mg doses of Butorphanol tartrate every 6 hours on days 2 through 6, 7 through 11, and 12 through 16, respectively. Safety assessment was performed on days 7, 12, and 17. Serial blood samples were collected on days 1, 6, 11, and 16, and the plasma was analyzed for unchanged Butorphanol by a validated and specific radioimmunoassay. Butorphanol was rapidly absorbed and peak levels in plasma were generally attained within 1 hour after the nasal administration. The values of maximum concentration, minimum concentration, and area under the concentration versus time curve from time zero to the dosing interval [AUC(0-τ)] increased as the administered dose increased in a dose-proportional manner. The values of AUC from time zero to infinity after a single dose of 2 mg Butorphanol tartrate, 10.9 ng · hr/ml, were identical to the values of AUC(0-τ) after a multiple administration of 2 mg dose, 10.4 ng · hr/ml. Mean elimination half-life value was 5.45 hours. Steady state was reached in fewer than eight doses when given every 6 hours. Transnasal Butorphanol was well tolerated by all subjects. After repeated administration of transnasal Butorphanol, no significant changes were observed in the nasal examination, which included evaluation of color, wetness, and thickness of nostril membrane, air flow, airway patency, and general nasal conditions. The findings of this phase I study indicate that transnasal Butorphanol is well tolerated, locally as well as systemically, and pharmacokinetics are linear within the expected therapeutic dose range. Clinical Pharmacology and Therapeutics (1993) 54, 34–41; doi:10.1038/clpt.1993.106
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The absolute bioavailability of transnasal Butorphanol in patients experiencing rhinitis.
European journal of clinical pharmacology, 1993Co-Authors: Wen Chyi Shyu, Kenneth A. Pittman, Donald S. Robinson, Rashmi H. BarbhaiyaAbstract:The absolute bioavailability (f) and pharmacokinetics of transnasal Butorphanol were evaluated in patients experiencing rhinitis. In an open three-way crossover study, a single 2-mg dose of Butorphanol tartrate was administered by intravenous bolus injection (Treatment A), by the transnasal route (Treatment B), or by the transnasal route with pretreatment of the vasoconstrictor, oxymetazoline (Treatment C). Plasma concentrations of Butorphanol were determined using a drug specific radioimmunoassay. The pharmacokinetic parameters were derived using the noncompartmental methods.
Kevin J. Volk - One of the best experts on this subject based on the ideXlab platform.
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Profiling impurities and degradants of Butorphanol tartrate using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry substructural techniques
Journal of Pharmaceutical and Biomedical Analysis, 1996Co-Authors: Kevin J. Volk, Robyn A. Rourick, Steven E. Klohr, Edward H. KernsAbstract:Abstract A rapid and systemic strategy based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural techniques was utilized to elucidate the degradation products of Butorphanol, the active ingredient in stadol® NS. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray mass spectrometry, and tandem mass spectrometry to rapidly and accurately elucidate structues of impurities and degradants. In these studies, several low-level degradation products were observed in long-term storage stability samples of bulk Butorphanol. The resulting analytical profile includes information on five degradants including molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. The degradation products formed during long-term storage of Butorphanol tartrate included oxidative products proposed as 9-hydroxy- and 9-keto-Butorphanol, norButorphanol, a ring-contraction degradant, and Δ1, 10α-Butorphanol. These methodologies are applicable at any stage of the drug product cycle from discovery through to development. This library of Butorphanol degradants provides a foundation for future development work regarding product monitoring, as well as a useful diagnosite tool for new degradation products.
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profiling impurities and degradants of Butorphanol tartrate using liquid chromatography mass spectrometry and liquid chromatography tandem mass spectrometry substructural techniques
Journal of Pharmaceutical and Biomedical Analysis, 1996Co-Authors: Kevin J. Volk, Robyn A. Rourick, Steven E. Klohr, Edward H. KernsAbstract:Abstract A rapid and systemic strategy based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural techniques was utilized to elucidate the degradation products of Butorphanol, the active ingredient in stadol® NS. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray mass spectrometry, and tandem mass spectrometry to rapidly and accurately elucidate structues of impurities and degradants. In these studies, several low-level degradation products were observed in long-term storage stability samples of bulk Butorphanol. The resulting analytical profile includes information on five degradants including molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. The degradation products formed during long-term storage of Butorphanol tartrate included oxidative products proposed as 9-hydroxy- and 9-keto-Butorphanol, norButorphanol, a ring-contraction degradant, and Δ1, 10α-Butorphanol. These methodologies are applicable at any stage of the drug product cycle from discovery through to development. This library of Butorphanol degradants provides a foundation for future development work regarding product monitoring, as well as a useful diagnosite tool for new degradation products.
Wen Chyi Shyu - One of the best experts on this subject based on the ideXlab platform.
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A Pharmacokinetic Interaction Study Between Butorphanol and Sumatriptan Nasal Sprays in Healthy Subjects: Importance of the Timing of Butorphanol Administration
Cephalalgia : an international journal of headache, 2002Co-Authors: Nimish N. Vachharajani, Wen Chyi Shyu, David W. BoultonAbstract:Sumatriptan and Butorphanol nasal sprays are commonly used agents for the management of migraine headaches. Under certain circumstances, these two agents may be administered closely in time. However, the possibility of a pharmacokinetic interaction and the safety of this regime have not been examined. In this crossover design study, 24 healthy subjects received the following four treatments, each separated by at least 7 days: 1 mg Butorphanol (Stadol NS7®); 20 mg sumatriptan (Imitrex® Nasal Spray); or both formulations together with Butorphanol administered either 1 or 30 min after sumatriptan. Serial plasma samples were collected for 24 h post-dose and analysed for Butorphanol and/or sumatriptan by HPLC-MS/MS. Butorphanol plasma concentrations were reduced when it was administered 1 min (mean 28.6% decrease in AUC0-∞), but not 30 min, after sumatriptan. The pharmacokinetics of sumatriptan were not substantially altered by Butorphanol. The combination of nasally administered sumatriptan and Butorphanol ap...
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Pharmacokinetic Interaction Between Butorphanol Nasal Spray and Oral Metoclopramide in Healthy Women
Journal of clinical pharmacology, 1997Co-Authors: Nimish N. Vachharajani, Wen Chyi Shyu, Rashmi H. BarbhaiyaAbstract:The pharmacokinetics of Butorphanol nasal spray, with and without the coadministration of metoclopramide, were studied in 24 healthy women. In this crossover study all volunteers received 3 treatments: a single, 1-mg dose of Butorphanol nasal spray, a single, 10-mg oral dose of metoclopramide, and a combination of a single, 1-mg dose of Butorphanol nasal spray and a single, 10-mg oral dose of metoclopramide. There was at least a one-week washout period between sessions. Serial blood samples were collected and plasma samples analyzed using a validated radioimmunoassay to determine the concentration of Butorphanol, or a high-performance liquid chromatography/ultraviolet procedure was used to determine the concentration of metoclopramide. There were no statistically significant differences in the pharmacokinetic parameters, Cmax, tmax, AUC, and t1/2, for Butorphanol with or without metoclopramide. Similarly, except for a delay in tmax of metoclopramide with coadministration of Butorphanol, the pharmacokinetic parameters of metoclopramide were not significantly different between two treatments. Thus, the pharmacokinetics of both Butorphanol and metoclopramide were not significantly altered when administered in combination. The incidence of nausea/vomiting after Butorphanol administration was substantially reduced by coadministration of metoclopramide. Based on the pharmacokinetic and safety results, it can be concluded that Butorphanol nasal spray and metoclopramide can be administered in combination without altering the dose regimen of either drug.
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Lack of pharmacokinetic interaction between Butorphanol tartrate nasal spray and sumatriptan succinate.
The Journal of Clinical Pharmacology, 1995Co-Authors: Nuggehally R. Srinivas, Wen Chyi Shyu, David H. Upmalis, Rashmi H. BarbhaiyaAbstract:The pharmacokinetics of Butorphanol tartrate given in a nasal spray with and without the co-administration of sumatriptan succinate were studied in 24 healthy men and women. In this crossover design study, all subjects received 2 treatments: a single 1-mg dose of Butorphanol nasal spray and a 1-mg dose of Butorphanol nasal spray plus a single 6-mg subcutaneous (SC) dose of sumatriptan. There was a two-week washout period between sessions. Serial blood samples were collected and plasma samples analyzed using validated radioimmunoassay and high-performance liquid chromatography/electrochemical procedures to determine the concentrations of unchanged Butorphanol and sumatriptan, respectively. There were no statistically significant differences for Butorphanol between the 2 treatments on any of the following pharmacokinetic parameters: Cmax, tmax, AUC, t1/2, CL/f, and Vz/f. Similarly, the pharmacokinetic parameters obtained for sumatriptan (given with Butorphanol nasal spray) were comparable with the literature values obtained for a single 6-mg SC dose of sumatriptan. These data show a lack of pharmacokinetic interaction between Butorphanol nasal spray and sumatriptan. Butorphanol nasal spray and sumatriptan were well tolerated. The adverse experience profiles of Butorphanol nasal spray were comparable between the treatments, with and without sumatriptan. It can be concluded that regimens of Butorphanol nasal spray and sumatriptan need not be changed for either pharmacokinetic or safety considerations when the two compounds are co-administered in treating acute migraine attacks.
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Multiple‐dose phase I study of transnasal Butorphanol
Clinical pharmacology and therapeutics, 1993Co-Authors: Wen Chyi Shyu, Kenneth A. Pittman, Donald S. Robinson, Rashmi H. BarbhaiyaAbstract:The safety, tolerance, and pharmacokinetics of transnasal Butorphanol were evaluated in a double-blind, multiple-dose phase I study. A total of 18 subjects received either placebo (n= 6) or a single transnasal dose of 2 mg Butorphanol tartrate on the first day and 1, 2, and 4 mg doses of Butorphanol tartrate every 6 hours on days 2 through 6, 7 through 11, and 12 through 16, respectively. Safety assessment was performed on days 7, 12, and 17. Serial blood samples were collected on days 1, 6, 11, and 16, and the plasma was analyzed for unchanged Butorphanol by a validated and specific radioimmunoassay. Butorphanol was rapidly absorbed and peak levels in plasma were generally attained within 1 hour after the nasal administration. The values of maximum concentration, minimum concentration, and area under the concentration versus time curve from time zero to the dosing interval [AUC(0-τ)] increased as the administered dose increased in a dose-proportional manner. The values of AUC from time zero to infinity after a single dose of 2 mg Butorphanol tartrate, 10.9 ng · hr/ml, were identical to the values of AUC(0-τ) after a multiple administration of 2 mg dose, 10.4 ng · hr/ml. Mean elimination half-life value was 5.45 hours. Steady state was reached in fewer than eight doses when given every 6 hours. Transnasal Butorphanol was well tolerated by all subjects. After repeated administration of transnasal Butorphanol, no significant changes were observed in the nasal examination, which included evaluation of color, wetness, and thickness of nostril membrane, air flow, airway patency, and general nasal conditions. The findings of this phase I study indicate that transnasal Butorphanol is well tolerated, locally as well as systemically, and pharmacokinetics are linear within the expected therapeutic dose range. Clinical Pharmacology and Therapeutics (1993) 54, 34–41; doi:10.1038/clpt.1993.106
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The absolute bioavailability of transnasal Butorphanol in patients experiencing rhinitis.
European journal of clinical pharmacology, 1993Co-Authors: Wen Chyi Shyu, Kenneth A. Pittman, Donald S. Robinson, Rashmi H. BarbhaiyaAbstract:The absolute bioavailability (f) and pharmacokinetics of transnasal Butorphanol were evaluated in patients experiencing rhinitis. In an open three-way crossover study, a single 2-mg dose of Butorphanol tartrate was administered by intravenous bolus injection (Treatment A), by the transnasal route (Treatment B), or by the transnasal route with pretreatment of the vasoconstrictor, oxymetazoline (Treatment C). Plasma concentrations of Butorphanol were determined using a drug specific radioimmunoassay. The pharmacokinetic parameters were derived using the noncompartmental methods.
Steven E. Klohr - One of the best experts on this subject based on the ideXlab platform.
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Profiling impurities and degradants of Butorphanol tartrate using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry substructural techniques
Journal of Pharmaceutical and Biomedical Analysis, 1996Co-Authors: Kevin J. Volk, Robyn A. Rourick, Steven E. Klohr, Edward H. KernsAbstract:Abstract A rapid and systemic strategy based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural techniques was utilized to elucidate the degradation products of Butorphanol, the active ingredient in stadol® NS. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray mass spectrometry, and tandem mass spectrometry to rapidly and accurately elucidate structues of impurities and degradants. In these studies, several low-level degradation products were observed in long-term storage stability samples of bulk Butorphanol. The resulting analytical profile includes information on five degradants including molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. The degradation products formed during long-term storage of Butorphanol tartrate included oxidative products proposed as 9-hydroxy- and 9-keto-Butorphanol, norButorphanol, a ring-contraction degradant, and Δ1, 10α-Butorphanol. These methodologies are applicable at any stage of the drug product cycle from discovery through to development. This library of Butorphanol degradants provides a foundation for future development work regarding product monitoring, as well as a useful diagnosite tool for new degradation products.
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profiling impurities and degradants of Butorphanol tartrate using liquid chromatography mass spectrometry and liquid chromatography tandem mass spectrometry substructural techniques
Journal of Pharmaceutical and Biomedical Analysis, 1996Co-Authors: Kevin J. Volk, Robyn A. Rourick, Steven E. Klohr, Edward H. KernsAbstract:Abstract A rapid and systemic strategy based on liquid chromatography/mass spectrometry (LC/MS) profiling and liquid chromatography/tandem mass spectrometry (LC/MS/MS) substructural techniques was utilized to elucidate the degradation products of Butorphanol, the active ingredient in stadol® NS. This strategy integrates, in a single instrumental approach, analytical HPLC, UV detection, full-scan electrospray mass spectrometry, and tandem mass spectrometry to rapidly and accurately elucidate structues of impurities and degradants. In these studies, several low-level degradation products were observed in long-term storage stability samples of bulk Butorphanol. The resulting analytical profile includes information on five degradants including molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. The degradation products formed during long-term storage of Butorphanol tartrate included oxidative products proposed as 9-hydroxy- and 9-keto-Butorphanol, norButorphanol, a ring-contraction degradant, and Δ1, 10α-Butorphanol. These methodologies are applicable at any stage of the drug product cycle from discovery through to development. This library of Butorphanol degradants provides a foundation for future development work regarding product monitoring, as well as a useful diagnosite tool for new degradation products.
