Pharmaceutical Research and Development (R&D) is a 'knowledge intensive' business, requir... more Pharmaceutical Research and Development (R&D) is a 'knowledge intensive' business, requiring frequent and comprehensive knowledge transactions. One necessary class of knowledge transactions concerns the constant evaluation of incoming data from experiments, discussion of the data amongst scientists and physicians and the ability to make informed operational and strategic decisions amidst some uncertainty, particularly in the early phase of development. Because of these uncertainties, it is important to constantly review decisions to verify their validity as a drug development project moves on. As the decision-making is inextricably bound to appropriate risk awareness and risk management, the consideration of options and appropriate scenario planning, the application of past experience to present information should help provide a balanced assessment of risks prior to decision making. Experienced employees often immediately apply what they remember of their past experience to ...
Computers in Cardiology 1999. Vol.26 (Cat. No.99CH37004), 1999
... We found a 2nd to 3rd order Gabor spectrogram useful for the analysis of HRV data. We would l... more ... We found a 2nd to 3rd order Gabor spectrogram useful for the analysis of HRV data. We would like to promote JTF analysis of heart rate variability in clinical pharmacology to gain insight into the complex ANS regulation and ANS response to drugs. ...
Investigation of heart rate variability is the subject of considerable interest in physiology, cl... more Investigation of heart rate variability is the subject of considerable interest in physiology, clinical medicine, and clinical pharmacology. The functional assessment of the autonomic nerve system by observation of its main actors, the sympathetic and parasympathetic branch, is emphasizing the importance of autonomic regulation under different physiological circumstances, in several disease states, and under drug therapy. This paper describes a PC-based system designed with LabView that performs time-domain and frequency-domain analyses of heart rate variability as suggested by the guidelines of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Examples for heart rate variability are given for different physiological states along with an analysis and evaluation by the system described.
Int. Journal of Clinical Pharmacology and Therapeutics, 1970
To investigate whether systemic exposure to desisobutyrylciclesonide (des-CIC) (the pharmacologic... more To investigate whether systemic exposure to desisobutyrylciclesonide (des-CIC) (the pharmacologically active metabolite of ciclesonide) and erythromycin are affected by combined administration of ciclesonide and erythromycin. 18 healthy subjects were enrolled in a Phase 1, open-label, randomized, three-period crossover study. Each subject received ciclesonide (640 microg ex-actuator, equivalent to 800 microg ex-valve, via hydrofluoroalkane metered-dose inhaler) and erythromycin (500 mg PO), separately and in combination, in random order. Blood samples were collected at timed intervals to determine serum concentrations of erythromycin, des-CIC, and ciclesonide using HPLC-MS detection. Adverse events were recorded throughout the study. Combined administration of ciclesonide and erythromycin did not alter the pharmacokinetics (PK) of either drug. The serum concentration vs. time profiles of erythromycin, des-CIC, and ciclesonide were similar when ciclesonide and erythromycin were administered separately or together. In addition, the PK characteristics of erythromycin and des-CIC were equivalent following single or co-administration. Point estimates (90% confidence intervals (CI)) for erythromycin were as follows: AUC0-inf, 0.96 (0.79, 1.18); Cmax, 1.00 (0.84, 1.20); and t1/2, 0.96 (0.83, 1.12). The following point estimates (90% CI) were obtained for des-CIC: AUC0-inf, 1.16 (1.03, 1.30); Cmax, 1.06 (0.98, 1.15); and t1/2, 1.04 (0.96, 1.13). Lack of ciclesonide/erythromycin interaction was demonstrated as the 90% CI of AUC0-inf, Cmax, and t1/2 of both compounds were entirely within the stipulated equivalence range of 0.67 - 1.50. No study drug-related adverse events occurred during this study. Combined administration of ciclesonide and erythromycin did not alter the PK properties of either drug. Both drugs were safe and well-tolerated. Therefore, systemic exposure to ciclesonide or erythromycin is not increased in patients receiving concomitant therapy.
The primary aim of the present study was to investigate the effect of ketoconazole on the pharmac... more The primary aim of the present study was to investigate the effect of ketoconazole on the pharmacokinetics of nisoldipine. A single dose of nisoldipine 5 mg immediate-release tablet was administered either alone or in combination with ketoconazole 200 mg (4 days pretreatment and concomitant administration) in a randomized crossover trial in seven healthy male Caucasian volunteers. Plasma concentration-versus-time profiles of nisoldipine and its metabolite M9 were determined. Pre-treatment with and concomitant administration of ketoconazole resulted in a 24-fold and 11-fold, increase in mean AUC and Cmax of nisoldipine, respectively, compared with treatment with nisoldipine 5 mg alone. The ketoconazole-induced increase in plasma concentration of the metabolite M9 was of similar magnitude. The interaction is attributed to inhibition of cytochrome 3A4-mediated first-pass metabolism. Ketoconazole and other antifungal drugs of the substituted imidazole type as well as other potent inhibitors of cytochrome 3A4 should not be used concomitantly with nisoldipine.
An edge-sensitive noise reduction algorithm for digital image processing is proposed. It is desig... more An edge-sensitive noise reduction algorithm for digital image processing is proposed. It is designed as C-DLL to run as a macro command under Image-Pro Plus. Its properties are compared to the median filter and a simple smoothing kernel.
Inhaled medicines are designed mainly to provide safe and efficacious treatment of respiratory di... more Inhaled medicines are designed mainly to provide safe and efficacious treatment of respiratory diseases, offering the potential advantages of targeted drug delivery such as reduced onset time and increased therapeutic ratio. However, as a flipside of targeted drug delivery, drug levels in the relevant effect compartment cannot be easily assessed. In combination with technical challenges associated with aerosolizing and administering an inhaled medicine, this renders inhalation product development demanding in the regulatory aspect as well. Emerging technologies that could address some of these challenges include (i) mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modeling, which in combination with experimental techniques such as positron emission tomography could provide information on local target engagement; (ii) patient-feedback features in combination with electronic monitoring, which may improve patient adherence as well as patient handling; and (iii) controlled-release formulations and nanotechnology-based formulations with high drug load, which may expand the scope of development of compounds and targets suitable for inhalation product development.
Pharmaceutical Research and Development (R&D) is a 'knowledge intensive' business, requir... more Pharmaceutical Research and Development (R&D) is a 'knowledge intensive' business, requiring frequent and comprehensive knowledge transactions. One necessary class of knowledge transactions concerns the constant evaluation of incoming data from experiments, discussion of the data amongst scientists and physicians and the ability to make informed operational and strategic decisions amidst some uncertainty, particularly in the early phase of development. Because of these uncertainties, it is important to constantly review decisions to verify their validity as a drug development project moves on. As the decision-making is inextricably bound to appropriate risk awareness and risk management, the consideration of options and appropriate scenario planning, the application of past experience to present information should help provide a balanced assessment of risks prior to decision making. Experienced employees often immediately apply what they remember of their past experience to ...
Computers in Cardiology 1999. Vol.26 (Cat. No.99CH37004), 1999
... We found a 2nd to 3rd order Gabor spectrogram useful for the analysis of HRV data. We would l... more ... We found a 2nd to 3rd order Gabor spectrogram useful for the analysis of HRV data. We would like to promote JTF analysis of heart rate variability in clinical pharmacology to gain insight into the complex ANS regulation and ANS response to drugs. ...
Investigation of heart rate variability is the subject of considerable interest in physiology, cl... more Investigation of heart rate variability is the subject of considerable interest in physiology, clinical medicine, and clinical pharmacology. The functional assessment of the autonomic nerve system by observation of its main actors, the sympathetic and parasympathetic branch, is emphasizing the importance of autonomic regulation under different physiological circumstances, in several disease states, and under drug therapy. This paper describes a PC-based system designed with LabView that performs time-domain and frequency-domain analyses of heart rate variability as suggested by the guidelines of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Examples for heart rate variability are given for different physiological states along with an analysis and evaluation by the system described.
Int. Journal of Clinical Pharmacology and Therapeutics, 1970
To investigate whether systemic exposure to desisobutyrylciclesonide (des-CIC) (the pharmacologic... more To investigate whether systemic exposure to desisobutyrylciclesonide (des-CIC) (the pharmacologically active metabolite of ciclesonide) and erythromycin are affected by combined administration of ciclesonide and erythromycin. 18 healthy subjects were enrolled in a Phase 1, open-label, randomized, three-period crossover study. Each subject received ciclesonide (640 microg ex-actuator, equivalent to 800 microg ex-valve, via hydrofluoroalkane metered-dose inhaler) and erythromycin (500 mg PO), separately and in combination, in random order. Blood samples were collected at timed intervals to determine serum concentrations of erythromycin, des-CIC, and ciclesonide using HPLC-MS detection. Adverse events were recorded throughout the study. Combined administration of ciclesonide and erythromycin did not alter the pharmacokinetics (PK) of either drug. The serum concentration vs. time profiles of erythromycin, des-CIC, and ciclesonide were similar when ciclesonide and erythromycin were administered separately or together. In addition, the PK characteristics of erythromycin and des-CIC were equivalent following single or co-administration. Point estimates (90% confidence intervals (CI)) for erythromycin were as follows: AUC0-inf, 0.96 (0.79, 1.18); Cmax, 1.00 (0.84, 1.20); and t1/2, 0.96 (0.83, 1.12). The following point estimates (90% CI) were obtained for des-CIC: AUC0-inf, 1.16 (1.03, 1.30); Cmax, 1.06 (0.98, 1.15); and t1/2, 1.04 (0.96, 1.13). Lack of ciclesonide/erythromycin interaction was demonstrated as the 90% CI of AUC0-inf, Cmax, and t1/2 of both compounds were entirely within the stipulated equivalence range of 0.67 - 1.50. No study drug-related adverse events occurred during this study. Combined administration of ciclesonide and erythromycin did not alter the PK properties of either drug. Both drugs were safe and well-tolerated. Therefore, systemic exposure to ciclesonide or erythromycin is not increased in patients receiving concomitant therapy.
The primary aim of the present study was to investigate the effect of ketoconazole on the pharmac... more The primary aim of the present study was to investigate the effect of ketoconazole on the pharmacokinetics of nisoldipine. A single dose of nisoldipine 5 mg immediate-release tablet was administered either alone or in combination with ketoconazole 200 mg (4 days pretreatment and concomitant administration) in a randomized crossover trial in seven healthy male Caucasian volunteers. Plasma concentration-versus-time profiles of nisoldipine and its metabolite M9 were determined. Pre-treatment with and concomitant administration of ketoconazole resulted in a 24-fold and 11-fold, increase in mean AUC and Cmax of nisoldipine, respectively, compared with treatment with nisoldipine 5 mg alone. The ketoconazole-induced increase in plasma concentration of the metabolite M9 was of similar magnitude. The interaction is attributed to inhibition of cytochrome 3A4-mediated first-pass metabolism. Ketoconazole and other antifungal drugs of the substituted imidazole type as well as other potent inhibitors of cytochrome 3A4 should not be used concomitantly with nisoldipine.
An edge-sensitive noise reduction algorithm for digital image processing is proposed. It is desig... more An edge-sensitive noise reduction algorithm for digital image processing is proposed. It is designed as C-DLL to run as a macro command under Image-Pro Plus. Its properties are compared to the median filter and a simple smoothing kernel.
Inhaled medicines are designed mainly to provide safe and efficacious treatment of respiratory di... more Inhaled medicines are designed mainly to provide safe and efficacious treatment of respiratory diseases, offering the potential advantages of targeted drug delivery such as reduced onset time and increased therapeutic ratio. However, as a flipside of targeted drug delivery, drug levels in the relevant effect compartment cannot be easily assessed. In combination with technical challenges associated with aerosolizing and administering an inhaled medicine, this renders inhalation product development demanding in the regulatory aspect as well. Emerging technologies that could address some of these challenges include (i) mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modeling, which in combination with experimental techniques such as positron emission tomography could provide information on local target engagement; (ii) patient-feedback features in combination with electronic monitoring, which may improve patient adherence as well as patient handling; and (iii) controlled-release formulations and nanotechnology-based formulations with high drug load, which may expand the scope of development of compounds and targets suitable for inhalation product development.
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