TY - JOUR
T1 - Recombinant human parathyroid hormone 1-34
T2 - Pharmacokinetics, tissue distribution and excretion in rats
AU - Hu, Zeping
AU - Niu, Huisheng
AU - Yang, Xiaoxia
AU - Li, Huaifen
AU - Sang, Guowei
AU - Li, Bo
N1 - Funding Information:
The authors gratefully acknowledge Southwestern China Biotech Pilot Base Co. Ltd. for providing the rhPTH (1–34). This work was funded by the Academic Research Funds of National Institute for the Control of Pharmaceutical and Biological Products, PR China.
PY - 2006/7/24
Y1 - 2006/7/24
N2 - 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 125I-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 125I-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 3.4-4.1 h, 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 72 h postdosing, respectively; whereas 6% excreted into bile up to 24 h 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.
AB - 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 125I-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 125I-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 3.4-4.1 h, 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 72 h postdosing, respectively; whereas 6% excreted into bile up to 24 h 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.
KW - Bioavailability
KW - Distribution
KW - Excretion
KW - Pharmacokinetics
KW - Recombinant human parathyroid hormone (1-34)
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U2 - 10.1016/j.ijpharm.2006.03.005
DO - 10.1016/j.ijpharm.2006.03.005
M3 - Article
C2 - 16621369
AN - SCOPUS:33745220955
SN - 0378-5173
VL - 317
SP - 144
EP - 154
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 2
ER -