Pharmacokinetics and Hepatic Extraction of Recombinant Human Parathyroid Hormone, hPTH (1–34), in Rat, Dog, and Monkey

Jones, Karen O.; Owusu-Ababio, Godfried; Vick, Andrew; Khan, Mubeena

doi:10.1002/jps.20720

Cited by 8 publications

(2 citation statements)

References 16 publications

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“…Observed concentrations and PK analyses resulting from intravenous administration of PTH(1–34) agree well with those reported by Jones et al who evaluated the same 10 μg/kg (2.4 nmol/kg) bolus dose that we used. Their estimate of clearance (98 mL/(min×kg)) agrees well with ours (83 mL/(min×kg)) using an average body weight of 0.3 kg).…”

Section: Discussionsupporting

confidence: 87%

Pharmacokinetics in Rats of a Long-Acting Human Parathyroid Hormone–Collagen Binding Domain Peptide Construct

Stratford

Sakon

et al. 2014

Journal of Pharmaceutical Sciences

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The pharmacokinetics of a hybrid peptide consisting of the N-terminal biologically active region of human parathyroid hormone (PTH) linked to a collagen binding domain (CBD) were evaluated in female Sprague-Dawley rats. The peptide, PTH-CBD, consists of the first 33 amino acids of PTH linked as an extension of the amino acid chain to the CBD peptide derived from ColH collagenase of Clostridium histolyticum. Serum concentrations arising from single dose administration by the subcutaneous and intravenous routes were compared to those measured following route specific mole equivalent doses of PTH(1-34). Population-based modeling demonstrated similar systemic absorption kinetics and bioavailability for both peptides. Exposure to PTH-CBD was 6-fold higher due to a systemic clearance of approximately 20% relative to PTH(1-34); however, these kinetics were consistent with >95% of a dose being eliminated from serum within 24 hours. Results obtained support continued investigation of PTH-CBD as a bone targeted anabolic agent for the treatment of post-menopausal osteoporosis.

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Section: Discussionsupporting

confidence: 87%

Pharmacokinetics in Rats of a Long-Acting Human Parathyroid Hormone–Collagen Binding Domain Peptide Construct

Stratford

Sakon

et al. 2014

Journal of Pharmaceutical Sciences

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“…Previously, the pharmacokinetics of rhPTH(1–34) had been extensively investigated in human beings [12–16], rats, dogs and monkeys [17,18]. After the subcutaneous administration of rhPTH(1–34) 10, 20 and 40 μg/kg in human beings, it was rapidly absorbed and reached the maximum plasma concentration after about 30 min., as well as rapidly eliminated with a half‐life ( t 1/2 ) of 1 hr [12,19].…”

mentioning

confidence: 99%

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Recombinant Human Parathyroid Hormone after Single‐ and Multiple‐Dose Subcutaneous Administration in Healthy Chinese Volunteers

Liu

Shi

et al. 2011

Basic Clin Pharma Tox

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Recombinant human parathyroid hormone ] represents a new class of anabolic agents for the treatment of osteoporosis. The present study was designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of rhPTH(1-84) after single-and multiple-dose subcutaneous administration in healthy Chinese volunteers. Six cohorts of 32 volunteers received a single dose of rhPTH(1-84) at 0.5-5.0 lg ⁄ kg, and two cohorts of 12 volunteers received 2.0 and 3.0 lg ⁄ kg of rhPTH(1-84) once daily for 7 consecutive days to assess its safety and tolerability. The results indicated that rhPTH(1-84) appeared to be safe and well tolerated. Additionally, pharmacokinetics of rhPTH (1-84) -84) and rhPTH(1-34) were found to be dose proportional. The pharmacokinetic parameters for rhPTH(1-84) and rhPTH(1-34) after administration of multiple doses of 2.0 lg ⁄ kg were as follows: C ss_max = (164.96 € 52.61) and (75.05 € 7.31) pg ⁄ mL; C ss_min = (6.99 € 7.73) and (2.05 € 2.82) pg ⁄ mL; AUC ss = (567.26 € 118.41) and (306.02 € 77.55) pg hr ⁄ mL; t 1 ⁄ 2 = (1.81 € 0.89) and (2.27 € 1.11) hr; DF = (6.93 € 2.64) and (6.00 € 1.37), respectively. After multiple doses, the pharmacokinetic parameters for rhPTH(1-84) were consistent with those after single dose. However, the mean C max and AUC 0-10 of rhPTH(1-34) after multiple dosing were significantly higher than the corresponding values obtained after single-dose administration. Serum total calcium and phosphate concentrations increased and decreased significantly at 4 hr post-dosing, respectively.

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Basic Aspects of PTH in Skeletal Health

Hock¹

2009

Osteoporosis

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Pharmacokinetics and Hepatic Extraction of Recombinant Human Parathyroid Hormone, hPTH (1–34), in Rat, Dog, and Monkey

Cited by 8 publications

References 16 publications

Pharmacokinetics in Rats of a Long-Acting Human Parathyroid Hormone–Collagen Binding Domain Peptide Construct

Pharmacokinetics in Rats of a Long-Acting Human Parathyroid Hormone–Collagen Binding Domain Peptide Construct

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Recombinant Human Parathyroid Hormone after Single‐ and Multiple‐Dose Subcutaneous Administration in Healthy Chinese Volunteers

Basic Aspects of PTH in Skeletal Health

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