Effect of recombinant porcine somatotropin (rpST) on drug disposition in swine.
Treatment of pigs with recombinant porcine somatotropin (rpST) causes a marked increase in feed utilization with increased weight-gain over untreated controls. Physiological parameters such as creatinine clearance were increased by rpST treatment. Clearance of drugs eliminated by hepatic extraction, like indocyanine green (ICG), were also increased by rpST treatment. However, clearance of intravenous (i.v.)-dosed propranolol (PPL) was not affected by rpST treatment and data from oral (p.o.)-dosing was inconclusive because of the low bioavailability, probably because of a high first-pass effect. The very low oral bioavailability indicates that intestinal metabolism of PPL is probably quite high. Analysis of urinary metabolites indicated production of the two phenolic isomers, but there was no metabolite corresponding to N-dealkylase activity; although the latter metabolite could have been eliminated in the bile with subsequent fecal elimination. PPL was an excellent in vitro substrate for measuring hepatic DME activity in vitro; two phenolic and one N-dealkylated metabolite were formed. The overall conclusions regarding this study must be that the effects of rpST on drug bioavailability and elimination were equivocal. As ICG and creatinine clearances were both increased significantly, one cannot rule out the probability that rpST would increase drug elimination in pigs as a result of increased hepatic uptake and/or renal clearance. One can only speculate that clearance of concurrently administered drugs would be increased. This would reduce residue levels, but it might also reduce efficacy.
Kawalek
J C
JC
Division of Animal Research, Office of Research, Center for Veterinary Medicine, US Food and Drug Administration, Laurel, MD 20708, USA. joseph.kawalek@fda.hhs.gov
Howard
K D
KD
D000818:Animals; D003404:Creatinine / Q000097:blood / Q000378:metabolism / Q000652:urine; D004347:Drug Interactions; D013006:Growth Hormone / Q000493:pharmacokinetics*; D007208:Indocyanine Green / Q000378:metabolism / Q000493:pharmacokinetics*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics*; D011994:Recombinant Proteins / Q000493:pharmacokinetics*; D013552:Swine / Q000097:blood / Q000652:urine
D011994:Recombinant Proteins; D013006:Growth Hormone; D011433:Propranolol; D003404:Creatinine; D007208:Indocyanine Green