title: Absorption and systemic availability of two synthetic growth hormone secretogogues and transport of glucose by the proximal small intestine of anestrus dogs after administering estradiol.
abstract: Pharmacokinetics for one growth hormone secretogogue (NNC 26-0722), but not for another (NN703), differ between dogs in estrus or anestrus. We examined if the differences could be mimicked by administering estradiol during anestrus and if there was a relationship with rates of small intestine absorption. Pharmacokinetics for oral doses of NN703 (1.0-1.6 mg kg(-1)) did not differ among dogs in estrus, anestrus, or anestrus and given estradiol for 1 week (days 1, 3, and 6; 40 micro g kg(-1)), whereas plasma concentrations of NNC 26-0722 increased from undetectable in untreated, anestrus dogs to several hundred nanograms per milliliter in dogs given estradiol, with maximal concentrations measured 5 min after oral dosage. Estradiol treatment increased small intestinal absorption of NNC 26-0722 by 100% (P<0.05), but did not increase absorption of NN703, and caused a 64% increase in carrier-mediated glucose transport at 50 mmol l(-1) (P<0.05) due to increased densities of transporters. These findings indicate estrus and estradiol enhance absorptive functions of the dog proximal small intestine and can affect pharmacokinetics for some orally administered drugs.
authors.affiliation: Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Maaloev, Denmark.
authors.forename: K K
authors.initials: KK
authors.lastname: Nielsen
authors.forename: K K
authors.initials: KK
authors.lastname: Buddington
authors.forename: K
authors.initials: K
authors.lastname: Raun
authors.forename: T K
authors.initials: TK
authors.lastname: Hansen
authors.forename: R K
authors.initials: RK
authors.lastname: Buddington
mesh_terms: D000284:Administration, Oral; D000780:Anestrus / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004151:Dipeptides / Q000493:pharmacokinetics*; D004285:Dogs; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D000074011:Peptide Transporter 1; D051269:Sodium-Glucose Transporter 1; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D004151:Dipeptides; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D000074011:Peptide Transporter 1; D051269:Sodium-Glucose Transporter 1; D027981:Symporters; D004958:Estradiol; D005947:Glucose; C120631:tabimorelin