Rik C. Schoemaker, Madelon M. Buijs1, Hanno Pijl1 and Adam F. Cohen
Centre for Human Drug Research and 1Department of General Internal Medicine, Leiden University Medical Center, The Netherlands
Metabolic substrate fluxes are generally estimated using the stable isotope method, where rates of appearance (Ra) are calculated using Steele’s equations. We demonstrate an alternative approach to estimate metabolic processes, and to determine relationships between hormones and their actions.
Growth hormone (GH) or saline was administered in a double-blind randomized crossover design to eight normal weight and eight obese subjects, and differences in the effects of GH on lipolysis were investigated. The relationship between GH and glycerol Ra (as an index of lipolysis) was described using pharmacokinetic/pharmacodynamic modeling. The model incorporated GH, glycerol, D5-glycerol and two sequential effect compartments to account for the delay in response. The estimated time-profile of glycerol Ra was compared with estimates obtained using Steele’s equations. The model adequately described both primary (i.e. glycerol) and derived (i.e. glycerol Ra) variables.
Modeling allowed the assessment of potential differences in GH sensitivity in the two groups, and indicated the importance of GH in lipolysis.
Reference: PAGE 10 (2001) Abstr 236 [www.page-meeting.org/?abstract=236]
Poster: poster