title: Growth hormone distribution kinetics are markedly reduced in adults with growth hormone deficiency.
abstract: OBJECTIVE
  Growth hormone (GH) circulating levels are highly dependent not only on GH secretion rate from the pituitary, but also on the hormone distribution in the compartments of the body and elimination phenomena. In adult GH-deficient patients these factors become critical nowadays, especially when recombinant human GH (rhGH) is available for replacement therapy. In the present study, we assess the influence of both distribution and elimination phenomena on GH pharmacokinetics in adult GH-deficient patients.
  
  
  METHODS
  We used a four-step methodology following a compartmental approach after an intravenous bolus of recombinant GH in adult GH-deficient patients.
  
  
  RESULTS
  We found that GH kinetics are clearly explained by a bi-exponential, two-compartmental model in GH-deficient patients, similarly than in normal or diabetic subjects, as previously shown. We have also observed a marked delay in the whole GH elimination process in GH-deficient patients compared to normal adult subjects, as revealed by metabolic clearance ratio (MCR), elimination constant from central compartment (k(10)), and mean resident time in the body (MRT). Interestingly, such a delay appear to be caused by deep changes in the distribution phase (Mtt(1)- mean transit time-1; T(1/2alpha)- GH half-life at distribution phase), while the elimination phenomenon remains unaltered.
  
  
  CONCLUSIONS
  Our results emphasize the relevance of distribution phenomena in GH pharmacokinetics, and indicates that studies avoiding data from the GH distribution phase, such as those carried out in steady-state conditions, or those using noncompartmental models, could easily miss relevant information. Our data should be taken into consideration when establishing the appropriate dosage for GH replacement treatments in GH-deficient patients, and calculations should include GH distribution kinetics.
authors.affiliation: Department of Endocrinology, Hospital Montecelo, Pontevedra, Spain.
authors.forename: Pablo F
authors.initials: PF
authors.lastname: Catalina
authors.forename: Concepción
authors.initials: C
authors.lastname: Páramo
authors.forename: Maria Amalia
authors.initials: MA
authors.lastname: Andrade
authors.forename: Federico
authors.initials: F
authors.lastname: Mallo
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors; D006207:Half-Life; D020249:Hormone Replacement Therapy / Q000379:methods*; D019382:Human Growth Hormone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D015282:Octreotide / Q000494:pharmacology; D013004:Somatostatin / Q000172:deficiency*
chemical_list: D019382:Human Growth Hormone; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone; D015282:Octreotide