Recombinant human parathyroid hormone 1-34: pharmacokinetics, tissue distribution and excretion in rats.
The objective of this work was to characterize the preclinical pharmacokinetics, tissue distribution, and excretion profiles of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)] in healthy rats. Pharmacokinetic properties of (125)I-rhPTH (1-34) were examined after a single subcutaneous (s.c.) and intravenous (i.v.) bolus injection, respectively. Tissue distribution and urinary, fecal, and biliary excretion patterns of (125)I-rhPTH (1-34) were also investigated following a single s.c. injection. Our results suggested that rhPTH (1-34) was rapidly distributed and cleared in a bi-exponential manner after a single i.v. bolus injection. Following a single s.c. administration, rhPTH (1-34) exhibited rapid and considerable absorption and declined in a mono-exponential manner, with the absolute bioavailability and elimination half-life of 65% and 3.4-4.1h, respectively. The TCA-precipitated radioactivity was widely distributed and rapidly diminished in most tissues/organs. Approximately 91% and 2% of the total radioactivity was recovered in urine and feces by 72h postdosing, respectively; whereas 6% excreted into bile up to 24h postdosing. These findings indicated high absolute bioavailability, rapid absorption and disposition of rhPTH (1-34) following a single s.c. administration in healthy rats. The accumulation of rhPTH (1-34) in tissues/organs examined appeared to be low. The major elimination route was urinary excretion.
Hu
Zeping
Z
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Republic of Singapore. zepinghu@nus.edu.sg
Niu
Huisheng
H
Yang
Xiaoxia
X
Li
Huaifen
H
Sang
Guowei
G
Li
Bo
B
D000818:Animals; D001646:Bile / Q000737:chemistry; D005243:Feces / Q000737:chemistry; D005260:Female; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007457:Iodine Radioisotopes; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011994:Recombinant Proteins