| 1. |
- Jauslin, Petra M, et al.
(author)
-
An integrated glucose-insulin model to describe oral glucose tolerance test data in type 2 diabetics
- 2007
-
In: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:10, s. 1244-1255
-
Journal article (peer-reviewed)abstract
- An integrated model for the glucose-insulin system describing oral glucose tolerance test data was developed, extending on a previously introduced model for intravenous glucose provocations. Model extensions comprised the description of glucose absorption by a chain of transit compartments with a mean transit time of 35 minutes, a bioavailability of 80%, and a representation of the incretin effect, expressed as a direct effect of the glucose absorption rate on insulin secretion. The ability of the model to predict the incretin effect was assessed by simulating the observed difference in insulin response following an oral glucose tolerance test compared with an isoglycemic glucose infusion mimicking an oral glucose tolerance test profile. The extension of the integrated glucose-insulin model to gain information from oral glucose tolerance test data considerably expands its range of applications because the oral glucose tolerance test is one of the most common glucose challenge experiments for assessing the efficacy of hypoglycemic agents in clinical drug development.
|
|
| 2. |
- Rayner, Craig R., et al.
(author)
-
Population pharmacokinetics of oseltamivir when coadministered with probenecid.
- 2008
-
In: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 48:8, s. 935-947
-
Journal article (peer-reviewed)abstract
- Oseltamivir is a potent, selective, oral neuraminidase inhibitor for the treatment and prophylaxis of influenza. Plasma concentrations of the active metabolite, oseltamivir carboxylate, are increased in the presence of probenecid, suggesting that the combination could allow for the use of reduced doses of oseltamivir. To investigate this proposal, we developed a population pharmacokinetic model and simulated the pharmacokinetics of candidate combination regimens of oral oseltamivir (45 mg and 30 mg twice a day) plus oral probenecid (500 mg/6 hourly). Probenecid plus oseltamivir 45 mg achieved all the pharmacokinetic parameters expected of oseltamivir alone, but combination with oseltamivir 30 mg and dose interval extension approaches did not. An oseltamivir-probenecid combination may compromise tolerability and enhance the potential for drug interactions. In addition, increased dosing requirements may affect compliance and attainment of optimal oseltamivir exposure, potentially facilitating the emergence of viral strains with reduced susceptibility to oseltamivir. These factors, set alongside increased capacity for oseltamivir production, should be carefully considered before an oseltamivir-probenecid combination is used.
|
|
| 3. |
- Silber, Hanna E, et al.
(author)
-
An integrated model for glucose and insulin regulation in healthy volunteers and type 2 diabetic patients following intravenous glucose provocations
- 2007
-
In: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:9, s. 1159-1171
-
Journal article (peer-reviewed)abstract
- An integrated model for the regulation of glucose and insulin concentrations following intravenous glucose provocations in healthy volunteers and type 2 diabetic patients was developed. Data from 72 individuals were included. Total glucose, labeled glucose, and insulin concentrations were determined. Simultaneous analysis of all data by nonlinear mixed effect modeling was performed in NONMEM. Integrated models for glucose, labeled glucose, and insulin were developed. Control mechanisms for regulation of glucose production, insulin secretion, and glucose uptake were incorporated. Physiologically relevant differences between healthy volunteers and patients were identified in the regulation of glucose production, elimination rate of glucose, and secretion of insulin. The model was able to describe the insulin and glucose profiles well and also showed a good ability to simulate data. The features of the present model are likely to be of interest for analysis of data collected in antidiabetic drug development and for optimization of study design.
|
|
| 4. |
- Smith, Mike K., et al.
(author)
-
Model Description Language (MDL) : A Standard for Modeling and Simulation
- 2017
-
In: CPT. - : WILEY. - 2163-8306. ; 6:10, s. 647-650
-
Journal article (peer-reviewed)abstract
- Recent work on Model Informed Drug Discovery and Development (MID3) has noted the need for clarity in model description used in quantitative disciplines such as pharmacology and statistics. 1-3 Currently, models are encoded in a variety of computer languages and are shared through publications that rarely include original code and generally lack reproducibility. The DDMoRe Model Description Language (MDL) has been developed primarily as a language standard to facilitate sharing knowledge and understanding of models.
|
|
