Recombinant human parathyroid hormone 1–34: Pharmacokinetics, tissue distribution and excretion in rats
| Autor: | Huisheng Niu, Guowei Sang, Huaifen Li, Zeping Hu, Bo Li, Xiaoxia Yang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Injections Subcutaneous Pharmaceutical Science Parathyroid hormone Absorption (skin) Urine Biology Iodine Radioisotopes Excretion Feces Pharmacokinetics Internal medicine medicine Animals Bile Distribution (pharmacology) Tissue Distribution Rats Wistar Peptide Fragments Recombinant Proteins Rats Bioavailability Endocrinology Parathyroid Hormone Injections Intravenous Female Hormone |
| Zdroj: | International Journal of Pharmaceutics. 317:144-154 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2006.03.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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