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Al Riyami, Sulaiman, Tang, Jonathan C Y 
ORCID: https://orcid.org/0000-0001-6305-6333, Galitzer, Hillel and Fraser, William
(2017)
Measurements of Osteoanabolic agents PTH (1-34) and PTHrP (1-36) in therapeutic studies and clinical diagnostics.
In: ASBMR 2017 Annual Meeting, 2017-09-08 - 2017-09-11, Colorado Convention Center, ASBMR Discovery Hall.
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Abstract
Background: Teriparatide PTH (1-34) is an osteoanabolic agent for treatment of osteoporosis. PTH (1-34) can also be used as replacement therapy in hypoparathyroidism and to accelerate fracture healing. Abaloparatide, PTHrP (1-36) analogue is a novel anabolic drug for treatment of osteoporosis. PTH (1-34) has also been used to assess response to PTH in conditions such as pseudohypoparathyroidism (PHP) (Ellsworth-Howard test (EHT)) Aims: To review the use of PTH (1-34) measurements in drug development studies, and in the diagnosis of patients with PHP. To highlight the potential use of measurement of PTHrP (1-36) using our LC-MS/MS method for measurement of intact PTHrP (1-36), intact PTH (1-34) and their respective oxidised forms simultaneously. Methods: Pharmacokinetic (PK) profiles from human subjects given either single subcutaneous (sc) injection of 20 ug Teriparatide (n=6) or 0.69 mg (n=4), 2.07 mg (n=6) oral PTH (1-34) (EnteraBio) were analysed using a validated LC-MS/MS method for intact/oxidised PTH (1-34). In EHT, urinary phosphate (spectrophotometric assay; Roche, Germany) and urine/plasma cyclic adenosine 3’,5’–monophosphate (cAMP) (LC-MS/MS) were performed on samples before and after 20ug sc adminstration of Teriparatide. Results/Discussion: PK profiles (Figure 1A) of oral PTH (1-34) showed a rapid absorption then rapid elimination. In contrast, teriparatide injection showed a slower rate of plasma clearance, possibly due to continuous absorption from the site of administration. Cmax was proportional to oral dosage given and the 2.07 mg of oral PTH (1-34) produced comparable Cmax to that produced by 20ug teriparatide injection (Figure 1B). We found the oxidised form of PTH (1-34) represent 20-30% of intact PTH (1-34) in the studied subjects. The EHT profile from a patient suspected of PHP showed a lack of cAMP response despite significant increase in plasma PTH (1-34) concentration. On the contrary, a post dose plasma cAMP concentration of >100 pmol/L and an increase from baseline level of urine cAMP exclude the diagnosis of PHP. Our LC-MS/MS PTHrP (1-36) assay produced a linear calibration curve from 10-2000 pg/mL (r2 >0.990), inter-/ intra-assay CV of <10% and a recovery of >98.6% (CV 3.6%). Conclusion: Our method for measurements of intact/oxidised form PTH (1-34) and PTHrP (1-36) can offer new insights into the therapeutic use of osteoanabolic agents, and the development of combination therapy with other anti-resorptive/anti-remodelling agents.
| Item Type: | Conference or Workshop Item (Poster) |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Depositing User: | Pure Connector |
| Date Deposited: | 16 Nov 2017 06:09 |
| Last Modified: | 19 Oct 2023 04:00 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/65478 |
| DOI: |
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