Pharmacokinetics of exogenous corticotropin in normal dogs, hospitalized dogs with non adrenal illness and adrenopathic dogs.

Abstract

Corticotropin (ACTH) pharmacokinetics was assessed in 10 normal dogs receiving exogenous ACTH (0.5 U/kg, i.v.). A two-compartment open model was most appropriate for description of exogenous ACTH pharmacokinetics. The apparent distribution and elimination rate constants (alpha and beta) were 7.4 +/- 2.7 x 10(-2) min(-1) and 5.5 +/- 3.8 x 10(-3) min(-1), respectively. Area under the concentration-time curve (AUC) was 2.91 +/- 0.78 x 10(4) pg x min/mL, mean residence time (MRT) was 45.0 +/- 12.2 min, the distribution half-life (t1/2alpha) was 9.4 min (harmonic mean), and the elimination half-life (t1/2beta) was 128 min (harmonic mean). The total body clearance of ACTH (ClB) was 1.83 +/- 0.46 x 10(4) mL x min/kg and volume of distribution (Vd(area)) was 30 +/- 15 L/kg. Corticotropin pharmacokinetics was also assessed in 12 client owned dogs, six dogs with non adrenal illness (NAI) and six dogs with hyperadrenocorticism (HAC), receiving exogenous ACTH (0.5 U/kg, i.v.). For these patients, data was best fitted to a one-compartment open model. In dogs with NAI, the AUC was 6.23 +/- 0.62 x 10(5) pg x min/mL, MRT was 38.7 +/- 12 min, the apparent elimination rate constant (k(el)) was 0.26 +/- 0.0017 min(-1) elimination half-life was 26.7 min, ClB was 0.84 +/- 0.1 x 10(4) mL/min/kg, and Vd(area) was 31.9 +/- 5.7 L/kg. In dogs with HAC, AUC was 4.74 +/- 0.23 x 10(5) pg x min/mL, MRT was 20.4 min, k(el) was 0.034 +/- 0.009 min(-1), half-life was 20.4 min, CIB was 1.06 +/- 6.0 x 10(4) mL/min/kg and Vd(area) was 29.7 +/- 6.7 L/kg. Dogs with pituitary-dependent hyperadrenocorticism showed more rapid elimination and clearance of exogenous corticotropin than dogs with NAI.