Pharmacokinetic-pharmacodynamic modelling of the hypoglycaemic effect of pulsatile administration of human insulin in rats
| Autor: | Mariko Hayata, Junya Nagai, Noriaki Samukawa, Makoto Miyazaki, Kazunori Iwanaga |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pulsatile flow
lcsh:Medicine 030209 endocrinology & metabolism Pharmacology 030226 pharmacology & pharmacy Models Biological Article 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Human insulin Medicine Animals Humans Hypoglycemic Agents Insulin lcsh:Science Multidisciplinary biology Pharmacokinetic pharmacodynamic business.industry Pharmaceutics lcsh:R Glucose transporter Hypoglycemia Rats Disease Models Animal Single bolus Pharmacodynamics biology.protein lcsh:Q Administration Intravenous Drug therapy business GLUT4 |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2045-2322 |
| Popis: | The relationship between the plasma insulin (INS) concentration–time course and plasma glucose concentration–time course during and after pulsatile INS administration to rats was characterized using a pharmacokinetic–pharmacodynamic (PK–PD) model. A total INS dose of 0.5 IU/kg was intravenously injected in 2 to 20 pulses over a 2-h period. Compared with the single bolus administration, the area under the effect-time curve (AUE) increased depending on the number of pulses, and the AUEs for more than four pulses plateaued at a significantly larger value, which was similar to that after the infusion of a total of 0.5 IU/kg of INS over 2 h. No increase in plasma INS concentration occurred after pulsatile administration. Two indirect response models primarily reflecting the receptor-binding process (IR model) or glucose transporter 4 (GLUT4) translocation (GT model) were applied to describe the PK–PD relationship after single intravenous bolus administration of INS. These models could not explain the observed data after pulsatile administration. However, the IR-GT model, which was a combination of the IR and GT models, successfully explained the effects of pulsatile administration and intravenous infusion. These results indicate that the receptor-binding process and GLUT4 translocation are responsible for the change in AUE after pulsatile administration. |
| Databáze: | OpenAIRE |
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