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Evan J. Begg - One of the best experts on this subject based on the ideXlab platform.
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The pharmacokinetics and pharmacogenetics of the antiemetic Cyclizine in palliative care patients.
Journal of Pain and Symptom Management, 2012Co-Authors: Jane Vella-brincat, Evan J. Begg, Berit P. Jensen, Paul K. L. Chin, Rebecca L Roberts, Mary Fairhall, Sandy Macleod, Kate ReidAbstract:Abstract Context Cyclizine, an antihistaminic antiemetic, is commonly used in palliative care. Its pharmacokinetics have been poorly studied, and its metabolic pathway is unknown but may involve the genetically controlled cytochrome P450 2D6 (CYP2D6). If this is the case, the metabolic ratio of Cyclizine to norCyclizine and efficacy/adverse effects may vary between patients according to their CYP2D6 genotype. Objectives To deduce the pharmacokinetics and antiemetic/sedative effects of Cyclizine and relate these and its metabolic ratio to the CYP2D6 genotype in palliative care patients. Methods Palliative care patients initiated on continuous Cyclizine subcutaneous (SC) infusions had blood samples taken and efficacy/toxicity scores measured during the approach to steady state. Another group of patients at steady state receiving oral Cyclizine had a single blood sample taken. Samples were analyzed to elucidate pharmacokinetic parameters and CYP2D6 genetics. Results SC dosing group: The median (interquartile range) Cyclizine half-life, volume of distribution, and clearance were 13 (7–48) hours, 23 (12–30)L/kg, and 15 (11–26)mL/min/kg, respectively. Nausea and sedation scores were 3.0 (1.2–5.7) and 5.0 (2.6–8.1), respectively, overall and did not vary with genotype ( P =0.76 and 0.11, respectively). The median overall metabolic ratio at steady state was 4.9 (3.8–9.2) and did vary with CYP2D6 genotype ( P =0.02). Oral dosing group: The median metabolic ratio was 2.1 (1.5–2.9) and did not vary with CYP2D6 genotype ( P =0.37). Conclusion Palliative care patients have similar Cyclizine pharmacokinetics to those reported in other patient groups. Cyclizine metabolism to norCyclizine may include CYP2D6 as the metabolic ratio varied with CYP2D6 genotype in the SC group.
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quantification of Cyclizine and norCyclizine in human plasma by liquid chromatography tandem mass spectrometry lc ms ms
Journal of Chromatography B, 2011Co-Authors: Berit P. Jensen, Jane Vellabrincat, Evan J. BeggAbstract:A rapid and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) assay was developed and validated for quantification of Cyclizine and its main metabolite norCyclizine in human plasma. Samples were prepared by protein precipitation with acetonitrile and cinnarizine was used as internal standard (recovery >87%). The analytes were eluted from a C8 50 mm × 2.0 mm analytical column using a linear gradient of methanol and 0.05% formic acid with a total analysis time of 4 min. Analytes were detected by MS/MS using electrospray ionisation in the positive mode with multiple reactions monitoring (MRM) of the precursor ion/product ion transitions 267.2/167.2 for Cyclizine and 253.2/167.2 for norCyclizine. Matrix effects were negligible. Standard curves for Cyclizine and norCyclizine were linear (r 2 ≥ 0.996) over the range 2–200 ng/mL, with 2 ng/mL representing the lower limit of quantification. Relative standard deviations were <14% for intra- and inter-day precision and the accuracy was within ±8%. The assay was successfully applied to a clinical study.
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Quantification of Cyclizine and norCyclizine in human plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS)
Journal of Chromatography B, 2011Co-Authors: Berit P. Jensen, Jane Vella-brincat, Evan J. BeggAbstract:A rapid and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) assay was developed and validated for quantification of Cyclizine and its main metabolite norCyclizine in human plasma. Samples were prepared by protein precipitation with acetonitrile and cinnarizine was used as internal standard (recovery >87%). The analytes were eluted from a C8 50 mm × 2.0 mm analytical column using a linear gradient of methanol and 0.05% formic acid with a total analysis time of 4 min. Analytes were detected by MS/MS using electrospray ionisation in the positive mode with multiple reactions monitoring (MRM) of the precursor ion/product ion transitions 267.2/167.2 for Cyclizine and 253.2/167.2 for norCyclizine. Matrix effects were negligible. Standard curves for Cyclizine and norCyclizine were linear (r 2 ≥ 0.996) over the range 2–200 ng/mL, with 2 ng/mL representing the lower limit of quantification. Relative standard deviations were
Berit P. Jensen - One of the best experts on this subject based on the ideXlab platform.
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The pharmacokinetics and pharmacogenetics of the antiemetic Cyclizine in palliative care patients.
Journal of Pain and Symptom Management, 2012Co-Authors: Jane Vella-brincat, Evan J. Begg, Berit P. Jensen, Paul K. L. Chin, Rebecca L Roberts, Mary Fairhall, Sandy Macleod, Kate ReidAbstract:Abstract Context Cyclizine, an antihistaminic antiemetic, is commonly used in palliative care. Its pharmacokinetics have been poorly studied, and its metabolic pathway is unknown but may involve the genetically controlled cytochrome P450 2D6 (CYP2D6). If this is the case, the metabolic ratio of Cyclizine to norCyclizine and efficacy/adverse effects may vary between patients according to their CYP2D6 genotype. Objectives To deduce the pharmacokinetics and antiemetic/sedative effects of Cyclizine and relate these and its metabolic ratio to the CYP2D6 genotype in palliative care patients. Methods Palliative care patients initiated on continuous Cyclizine subcutaneous (SC) infusions had blood samples taken and efficacy/toxicity scores measured during the approach to steady state. Another group of patients at steady state receiving oral Cyclizine had a single blood sample taken. Samples were analyzed to elucidate pharmacokinetic parameters and CYP2D6 genetics. Results SC dosing group: The median (interquartile range) Cyclizine half-life, volume of distribution, and clearance were 13 (7–48) hours, 23 (12–30)L/kg, and 15 (11–26)mL/min/kg, respectively. Nausea and sedation scores were 3.0 (1.2–5.7) and 5.0 (2.6–8.1), respectively, overall and did not vary with genotype ( P =0.76 and 0.11, respectively). The median overall metabolic ratio at steady state was 4.9 (3.8–9.2) and did vary with CYP2D6 genotype ( P =0.02). Oral dosing group: The median metabolic ratio was 2.1 (1.5–2.9) and did not vary with CYP2D6 genotype ( P =0.37). Conclusion Palliative care patients have similar Cyclizine pharmacokinetics to those reported in other patient groups. Cyclizine metabolism to norCyclizine may include CYP2D6 as the metabolic ratio varied with CYP2D6 genotype in the SC group.
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quantification of Cyclizine and norCyclizine in human plasma by liquid chromatography tandem mass spectrometry lc ms ms
Journal of Chromatography B, 2011Co-Authors: Berit P. Jensen, Jane Vellabrincat, Evan J. BeggAbstract:A rapid and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) assay was developed and validated for quantification of Cyclizine and its main metabolite norCyclizine in human plasma. Samples were prepared by protein precipitation with acetonitrile and cinnarizine was used as internal standard (recovery >87%). The analytes were eluted from a C8 50 mm × 2.0 mm analytical column using a linear gradient of methanol and 0.05% formic acid with a total analysis time of 4 min. Analytes were detected by MS/MS using electrospray ionisation in the positive mode with multiple reactions monitoring (MRM) of the precursor ion/product ion transitions 267.2/167.2 for Cyclizine and 253.2/167.2 for norCyclizine. Matrix effects were negligible. Standard curves for Cyclizine and norCyclizine were linear (r 2 ≥ 0.996) over the range 2–200 ng/mL, with 2 ng/mL representing the lower limit of quantification. Relative standard deviations were <14% for intra- and inter-day precision and the accuracy was within ±8%. The assay was successfully applied to a clinical study.
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Quantification of Cyclizine and norCyclizine in human plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS)
Journal of Chromatography B, 2011Co-Authors: Berit P. Jensen, Jane Vella-brincat, Evan J. BeggAbstract:A rapid and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) assay was developed and validated for quantification of Cyclizine and its main metabolite norCyclizine in human plasma. Samples were prepared by protein precipitation with acetonitrile and cinnarizine was used as internal standard (recovery >87%). The analytes were eluted from a C8 50 mm × 2.0 mm analytical column using a linear gradient of methanol and 0.05% formic acid with a total analysis time of 4 min. Analytes were detected by MS/MS using electrospray ionisation in the positive mode with multiple reactions monitoring (MRM) of the precursor ion/product ion transitions 267.2/167.2 for Cyclizine and 253.2/167.2 for norCyclizine. Matrix effects were negligible. Standard curves for Cyclizine and norCyclizine were linear (r 2 ≥ 0.996) over the range 2–200 ng/mL, with 2 ng/mL representing the lower limit of quantification. Relative standard deviations were
Lynne Hutchings - One of the best experts on this subject based on the ideXlab platform.
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drug combinations in syringe drivers the compatibility and stability of diamorphine with Cyclizine and haloperidol
Palliative Medicine, 1997Co-Authors: Paul F Grassby, Lynne HutchingsAbstract:The compatibility and stability of 28 combinations of diamorphine hydrochloride (5-100 mg/ml) with Cyclizine lactate (5-50 mg/ml), eight combinations of diamorphine (10-100 mg/ml) with haloperidol (2-4 mg/ml) and eight combinations of all three drugs was assessed after storage in 1 ml polypropylene syringes. Samples were stored for periods up to seven days in the light and at room temperature (22°C).Five combinations of diamorphine with Cyclizine precipitated immediately upon preparation. After analysis and determination of t90% values (the time taken for 10% degradation), 16 of the remaining 23 combinations were judged to be compatible (no signs of crystallization or precipitation) and stable (less than 10% loss of potency of either drug) after storage for 24 h. After seven days storage only four remained compatible and stable. The results indicate that ratios of diamorphine to Cyclizine of 1:1 are stable at concentrations up to 20 mg/ml. An increase in diamorphine concentration necessitates a reduction ...
Paul F Grassby - One of the best experts on this subject based on the ideXlab platform.
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drug combinations in syringe drivers the compatibility and stability of diamorphine with Cyclizine and haloperidol
Palliative Medicine, 1997Co-Authors: Paul F Grassby, Lynne HutchingsAbstract:The compatibility and stability of 28 combinations of diamorphine hydrochloride (5-100 mg/ml) with Cyclizine lactate (5-50 mg/ml), eight combinations of diamorphine (10-100 mg/ml) with haloperidol (2-4 mg/ml) and eight combinations of all three drugs was assessed after storage in 1 ml polypropylene syringes. Samples were stored for periods up to seven days in the light and at room temperature (22°C).Five combinations of diamorphine with Cyclizine precipitated immediately upon preparation. After analysis and determination of t90% values (the time taken for 10% degradation), 16 of the remaining 23 combinations were judged to be compatible (no signs of crystallization or precipitation) and stable (less than 10% loss of potency of either drug) after storage for 24 h. After seven days storage only four remained compatible and stable. The results indicate that ratios of diamorphine to Cyclizine of 1:1 are stable at concentrations up to 20 mg/ml. An increase in diamorphine concentration necessitates a reduction ...
Jane Vellabrincat - One of the best experts on this subject based on the ideXlab platform.
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quantification of Cyclizine and norCyclizine in human plasma by liquid chromatography tandem mass spectrometry lc ms ms
Journal of Chromatography B, 2011Co-Authors: Berit P. Jensen, Jane Vellabrincat, Evan J. BeggAbstract:A rapid and simple liquid chromatography-tandem mass spectrometry (LC–MS/MS) assay was developed and validated for quantification of Cyclizine and its main metabolite norCyclizine in human plasma. Samples were prepared by protein precipitation with acetonitrile and cinnarizine was used as internal standard (recovery >87%). The analytes were eluted from a C8 50 mm × 2.0 mm analytical column using a linear gradient of methanol and 0.05% formic acid with a total analysis time of 4 min. Analytes were detected by MS/MS using electrospray ionisation in the positive mode with multiple reactions monitoring (MRM) of the precursor ion/product ion transitions 267.2/167.2 for Cyclizine and 253.2/167.2 for norCyclizine. Matrix effects were negligible. Standard curves for Cyclizine and norCyclizine were linear (r 2 ≥ 0.996) over the range 2–200 ng/mL, with 2 ng/mL representing the lower limit of quantification. Relative standard deviations were <14% for intra- and inter-day precision and the accuracy was within ±8%. The assay was successfully applied to a clinical study.
