Pharmacokinetics and organ catabolism of cholecystokinin octapeptide in pigs.
The pharmacokinetics and organ catabolism of cholecystokinin octapeptide (CCK8) were studied in pigs. In conscious animals, intravenous infusion of increasing doses of CCK8 (2.9-232.3 pmol.kg-1.min-1) resulted in a linear increase of plasma CCK-like immunoreactivity (CCK-LI). At the cessation of infusion of the largest dose of CCK8, plasma CCK-LI promptly returned to near basal values. The half-disappearance time (t1/2), metabolic clearance rate (MCR) and distribution volume (DV) were estimated to be 0.55 +/- 0.03 min, 134.8 +/- 10.8 ml.kg-1.min-1 and 107.9 +/- 13.0 ml.kg-1, respectively. In another group of anesthetized animals, infusion of CCK8 at similar doses produced higher plateau plasma CCK levels and the t1/2, MCR and DV were calculated to be 0.68 +/- 0.06 min, 32.5 +/- 3.9 ml.kg-1.min-1 and 45.2 +/- 5.6 ml.kg-1, respectively. Estimates of first-pass immunological degradation through various vascular beds were in the range 27-66%, with in decreasing order the kidney, liver, hindleg, followed by the brain and gut. These results indicate that immunoreactive CCK8 is rapidly cleared from plasma during passage through several vascular beds. The peptide is only partly inactivated during hepatic transit and so may exert hormonal effects upon its release from intestinal stores.
Cuber
J C
JC
Laboratoire de Physiologie de la Nutrition, INRA-CNRZ, Jouy-en-Josas, France.
Bernard
C
C
Gibard
T
T
Chayvialle
J A
JA
D000818:Animals; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D009928:Organ Specificity; D011489:Protein Denaturation; D011863:Radioimmunoassay; D012844:Sincalide / Q000493:pharmacokinetics; D013552:Swine
D002766:Cholecystokinin; D012844:Sincalide