Single-dose subcutaneous administration of recombinant human parathyroid hormone [rhPTH(1-84)] in healthy postmenopausal volunteers

Background Parathyroid hormone [PTH(1–84)] is intended for treatment of osteoporosis because it stimulates new bone formation of normal structure and composition. Recently, recombinant human PTH(1–84) [rhPTH(1–84)] has become available for therapeutic evaluation. Objectives To assess the safety, tolerability, pharmacokinetics and pharmacodynamics of rhPTH(1–84) after single‐dose subcutaneous administration of rhPTH(1–84) or placebo to 32 healthy postmenopausal volunteers (dose range, 0.02 to 5.0 μg · kg−1). Results In the lower dose range (0.02 to 2.0 μg · kg−1), serum ionized and total calcium concentrations increased dose dependently, with approximately 0.15 mmol/L for dose levels >0.2 μg · kg−1 and >1.5 μg · kg−1, respectively, unlike the higher dose range (2.0 to 5.0 μg · kg−1), for which concentration‐time profiles clearly exhibited a biphasic pattern. Urine evaluation revealed an increase in both calcium/creatinine and phosphate/creatinine ratios, the former appearing in the 12‐ to 24‐hour and 24‐ to 36‐hour collections for doses >2.5 μg · kg−1 and the latter in the 0‐ to 12‐hour collection for doses ≥1.5 μg · kg−1. Urinary deoxypyridinoline excretion was used as a biochemical marker of bone resorption, but no consistent changes were found. Urinary cyclic adenosine monophosphate excretion, which is an indirect measure of PTH(1–84) action on the kidney, showed a clear increase in the 0‐ to 12‐hour urine collection for doses ≥1.5 μg · kg−1. As for ionized and total calcium, serum concentration‐time curves of PTH(1–84) exhibited a double‐peak profile, the first peak appearing about 5 to 10 minutes after administration and the second peak occurring about 1½ to 2 hours after administration. Serum terminal half‐life of PTH(1–84) was approximately 2½ hours. Conclusion Up to a dose of 5.0 μg · kg−1, rhPTH(1–84) was safe and well tolerated by healthy postmenopausal volunteers. Clinical Pharmacology & Therapeutics (1997) 61, 360–376; doi: