Gastric acid secretion induced by impromidine in the dog and man: analysis of dose-response relationships.
The new histamine H2-receptor agonist, impromidine, was used to assess three models of dose-response curves in vivo. Vm and ED50 values were calculated for gastric acid output to infusions of impromidine in the dog with a Heidenhain pouch and in man. In two models Michaelis-Menten kinetics were assumed: the linear transformation using the Eadie-Hofstee plot and the non-linear hyperbola, but in the third method the logistic function allowed the data to be analysed without making assumptions about the steepness of the curves. In the dog all three models gave similar results both for calculated Vm and ED50. Curve steepness from the logistic function was found to be 0.98 +/- 0.023 - not different from that assumed for the hyperbola (where steepness = 1). The results in man were different: the Eadie-Hofstee plot did not produce a significantly linear fit while the logistic function produced the smallest standard errors. The logistic curve slope was almost twice that assumed for the hyperbola (1.8 : 1) and it seems, therefore, that impromidine-induced gastric acid secretion does not follow Michaelis-Menten kinetics in man and data should be analysed using methods which allow the calculation of curve steepness.
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D017446:Impromidine; D007700:Kinetics; D008954:Models, Biological; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013045:Species Specificity
D006146:Guanidines; D007093:Imidazoles; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D017446:Impromidine