The Experts below are selected from a list of 18915 Experts worldwide ranked by ideXlab platform
Marlou L. P. S. Van Iersel - One of the best experts on this subject based on the ideXlab platform.
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A Population Pharmacokinetic Model for a Solid Oral Tablet Formulation of Posaconazole
Antimicrobial agents and chemotherapy, 2018Co-Authors: Marlou L. P. S. Van Iersel, Stefaan Rossenu, Rik De Greef, Hetty WaskinAbstract:A delayed-release solid Tablet Formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid Tablet Formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final pharmacokinetic model was used to simulate posaconazole exposure in patients at high risk for invasive fungal diseases treated with the proposed posaconazole dose of 300 mg twice daily on day 1, followed by 300 mg daily for 27 days. A one-compartment pharmacokinetic model with sequential zero-order and first-order absorption and a first-order disposition from the central compartment adequately described the pharmacokinetic profile of the posaconazole solid Tablet Formulation. Significant covariates included disease state (acute myeloid leukemia/myelodysplasia versus allogeneic hematopoietic stem cell transplantation), body weight, and Formulation on bioavailability; food status on first-order absorption rate; and dosing regimen (a single dose versus multiple doses) on clearance. Except for body weight, the impact of these covariates on posaconazole exposure was considered clinically irrelevant. This population pharmacokinetic analysis confirmed that the proposed dose of the posaconazole solid Tablet Formulation provides adequate target therapeutic exposure (>0.5 mg/liter) to a broad range of patients at high risk for invasive fungal disease.
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effect of a high fat meal on the pharmacokinetics of 300 milligram posaconazole in a solid oral Tablet Formulation
Antimicrobial Agents and Chemotherapy, 2015Co-Authors: Wendy M Kersemaekers, Rik De Greef, Hetty Waskin, Peter Dogterom, Eugene E Marcantonio, Marlou L. P. S. Van IerselAbstract:Posaconazole in oral suspension must be taken multiple times a day with food (preferably a high-fat meal) to ensure adequate exposure among patients. We evaluated the effect of food on the bioavailability of a new delayed-release Tablet Formulation of posaconazole at the proposed clinical dose of 300 mg once daily in a randomized, open-label, single-dose, two-period crossover study with 18 healthy volunteers. When a single 300-mg dose of posaconazole in Tablet form (3 Tablets × 100 mg) was administered with a high-fat meal, the posaconazole area under the concentration-time curve from 0 to 72 h (AUC0-72) and maximum concentration in plasma (Cmax) increased 51% and 16%, respectively, compared to those after administration in the fasted state. The median time to Cmax (Tmax) shifted from 5 h in the fasted state to 6 h under fed conditions. No serious adverse events were reported, and no subject discontinued the study due to an adverse event. Six of the 18 subjects reported at least one clinical adverse event; all of these events were mild and short lasting. The results of this study demonstrate that a high-fat meal only modestly increases the mean posaconazole exposure (AUC), ∼1.5-fold, after administration of posaconazole Tablets, in contrast to the 4-fold increase in AUC observed previously for a posaconazole oral suspension given with a high-fat meal.
C Sasikala - One of the best experts on this subject based on the ideXlab platform.
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development of uv spectrophotometry and rp hplc methods for the estimation of levosulpiride in bulk and in Tablet Formulation
Asian Journal of Research in Chemistry, 2010Co-Authors: S P Silambarasan, K Anandakumar, R Venkatalakshmi, C SasikalaAbstract:Two new simple, sensitive, rapid, accurate and precise methods, namely UV spectrophotometric and RP-HPLC methods were developed for the estimation of Levosulpiride in bulk and in Tablet Formulation. In UV spectrophotometric method, Levosulpiride exhibited maximum absorbance at 291.5 nm with apparent molar absorptivity of 2.6031 x 103 L mol−1 cm −1 in 0.1M HCl. Beer's law was obeyed in the concentration range of 10 -50 μg/ml. In RP-HPLC method, the elution was done using a mobile phase consisting of methanol and 25 mM phosphate buffer pH 3.5 (pH adjusted with phosphoric acid, 15:85 v/v) on Shimadzu HPLC C18 (4.6 x 150 mm) column at a flow rate of 0.8 ml/min with UV detection at 293 nm. An external standard calibration method was employed for quantization. The elution time was 5.08 minutes. Beer's law was found to be obeyed in the concentration range of 4 – 24 μg/ml. The results of proposed methods were validated statistically and by recovery studies. The % RSD values for recovery studies were found to be less than 2% for the both methods. Hence the proposed methods were successfully used to determine the drug content in bulk and in Tablet Formulation.
Hetty Waskin - One of the best experts on this subject based on the ideXlab platform.
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A Population Pharmacokinetic Model for a Solid Oral Tablet Formulation of Posaconazole
Antimicrobial agents and chemotherapy, 2018Co-Authors: Marlou L. P. S. Van Iersel, Stefaan Rossenu, Rik De Greef, Hetty WaskinAbstract:A delayed-release solid Tablet Formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid Tablet Formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final pharmacokinetic model was used to simulate posaconazole exposure in patients at high risk for invasive fungal diseases treated with the proposed posaconazole dose of 300 mg twice daily on day 1, followed by 300 mg daily for 27 days. A one-compartment pharmacokinetic model with sequential zero-order and first-order absorption and a first-order disposition from the central compartment adequately described the pharmacokinetic profile of the posaconazole solid Tablet Formulation. Significant covariates included disease state (acute myeloid leukemia/myelodysplasia versus allogeneic hematopoietic stem cell transplantation), body weight, and Formulation on bioavailability; food status on first-order absorption rate; and dosing regimen (a single dose versus multiple doses) on clearance. Except for body weight, the impact of these covariates on posaconazole exposure was considered clinically irrelevant. This population pharmacokinetic analysis confirmed that the proposed dose of the posaconazole solid Tablet Formulation provides adequate target therapeutic exposure (>0.5 mg/liter) to a broad range of patients at high risk for invasive fungal disease.
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effect of a high fat meal on the pharmacokinetics of 300 milligram posaconazole in a solid oral Tablet Formulation
Antimicrobial Agents and Chemotherapy, 2015Co-Authors: Wendy M Kersemaekers, Rik De Greef, Hetty Waskin, Peter Dogterom, Eugene E Marcantonio, Marlou L. P. S. Van IerselAbstract:Posaconazole in oral suspension must be taken multiple times a day with food (preferably a high-fat meal) to ensure adequate exposure among patients. We evaluated the effect of food on the bioavailability of a new delayed-release Tablet Formulation of posaconazole at the proposed clinical dose of 300 mg once daily in a randomized, open-label, single-dose, two-period crossover study with 18 healthy volunteers. When a single 300-mg dose of posaconazole in Tablet form (3 Tablets × 100 mg) was administered with a high-fat meal, the posaconazole area under the concentration-time curve from 0 to 72 h (AUC0-72) and maximum concentration in plasma (Cmax) increased 51% and 16%, respectively, compared to those after administration in the fasted state. The median time to Cmax (Tmax) shifted from 5 h in the fasted state to 6 h under fed conditions. No serious adverse events were reported, and no subject discontinued the study due to an adverse event. Six of the 18 subjects reported at least one clinical adverse event; all of these events were mild and short lasting. The results of this study demonstrate that a high-fat meal only modestly increases the mean posaconazole exposure (AUC), ∼1.5-fold, after administration of posaconazole Tablets, in contrast to the 4-fold increase in AUC observed previously for a posaconazole oral suspension given with a high-fat meal.
S P Silambarasan - One of the best experts on this subject based on the ideXlab platform.
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development of uv spectrophotometry and rp hplc methods for the estimation of levosulpiride in bulk and in Tablet Formulation
Asian Journal of Research in Chemistry, 2010Co-Authors: S P Silambarasan, K Anandakumar, R Venkatalakshmi, C SasikalaAbstract:Two new simple, sensitive, rapid, accurate and precise methods, namely UV spectrophotometric and RP-HPLC methods were developed for the estimation of Levosulpiride in bulk and in Tablet Formulation. In UV spectrophotometric method, Levosulpiride exhibited maximum absorbance at 291.5 nm with apparent molar absorptivity of 2.6031 x 103 L mol−1 cm −1 in 0.1M HCl. Beer's law was obeyed in the concentration range of 10 -50 μg/ml. In RP-HPLC method, the elution was done using a mobile phase consisting of methanol and 25 mM phosphate buffer pH 3.5 (pH adjusted with phosphoric acid, 15:85 v/v) on Shimadzu HPLC C18 (4.6 x 150 mm) column at a flow rate of 0.8 ml/min with UV detection at 293 nm. An external standard calibration method was employed for quantization. The elution time was 5.08 minutes. Beer's law was found to be obeyed in the concentration range of 4 – 24 μg/ml. The results of proposed methods were validated statistically and by recovery studies. The % RSD values for recovery studies were found to be less than 2% for the both methods. Hence the proposed methods were successfully used to determine the drug content in bulk and in Tablet Formulation.
N Mishra - One of the best experts on this subject based on the ideXlab platform.
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spectrophotometric method for simultaneous estimation of paracetamol and domperidone in Tablet Formulation
Asian Journal of Research in Chemistry, 2009Co-Authors: Kapil Kalra, S Naik, Garima Jarmal, N MishraAbstract:The development of Vireodt's method for simultaneous estimation of paracetamol and domperidone involves absorbance measurement at 250 nm and 285 nm corresponding to the respective absorption maxima. Both the drugs obey Beer Lambert's law in the range of 5–30 μg/ml for paracetamol and 0.8–5 μg/ml for domperidone. The Tablet Formulation (Grenil, KAPL) was evaluated for the percent content of both the drugs at the selected wavelengths. The method developed was validated to determine its accuracy, precision, specificity and ruggedness. The recovery study was carried out by standard addition method. The average percent recovery was found to be 99.45±0.47 for paracetamol and 100.67±0.18 for domperidone
