title: PTH(1-84) replacement therapy in hypoparathyroidism: a randomized controlled trial on pharmacokinetic and dynamic effects after 6 months of treatment.
abstract: Untreated, hypoparathyroidism (hypoPT) is a state of hypocalcemia with inappropriately low plasma parathyroid hormone (PTH) levels and hyperphosphatemia. PTH administration normalizes plasma calcium and phosphate levels and reduces the doses of calcium and active vitamin D analogues needed. To develop an evidence-based clinical algorithm to monitor hypoPT patients treated with recombinant human PTH (rhPTH[1-84]) injected subcutaneously in the thigh, we performed a 24-hour monitoring study of pharmacokinetic and pharmacodynamic effects in a group of 38 patients who had completed a 6-month randomized study on effects of treatment with a fixed rhPTH(1-84) dose of 100 µg/d or similar placebo as an add-on to conventional treatment. PTH levels rose immediately, reaching a median peak level of 26.5 (interquartile range [IQR], 20.1-42.5) pmol/L 15 minutes following injection. Thereafter, levels gradually decreased until reaching predosing levels after 16 hours, with a plasma half-life of 2.2 (1.7-2.5) hours. rhPTH(1-84) changed the diurnal rhythms of ionized calcium levels and 1,25-dihydroxyvitamin D (1,25[OH]2 D) levels, with rising levels following injection. Ionized calcium peaked after 7.0 (5.0-10.0) hours. Asymptomatic hypercalcemia was present in 71% of the rhPTH(1-84)-treated patients. Compared with placebo, 24-hour urinary calcium, phosphate, and magnesium did not change, although the diurnal variation in renal excretion rates changed significantly in response to treatment. In conclusion, as a safety precaution, we recommend occasionally measuring calcium levels at approximately 7 hours after administration in order to reveal episodes of hypercalcemia. A 100-µg daily dose of rhPTH(1-84) appears to be too high in some patients, suggesting a need for a device allowing for individual dose adjustments.
authors: Department of Endocrinology and Internal Medicine, MEA, Aarhus University Hospital, Aarhus, Denmark.
authors: Tanja
authors: T
authors: Sikjaer
authors: Anne Kristine
authors: AK
authors: Amstrup
authors: Lars
authors: L
authors: Rolighed
authors: Soren Geill
authors: SG
authors: Kjaer
authors: Leif
authors: L
authors: Mosekilde
authors: Lars
authors: L
authors: Rejnmark
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D008274:Magnesium / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D008274:Magnesium
keywords: CALCIUM/PHOSPHATE DISORDERS; CLINICAL TRIALS; HORMONES AND RECEPTORS; HYPOPARATHYROIDISM; METABOLISM; PARATHYROID GLAND; PARATHYROID HORMONE; PARATHYROID-RELATED DISORDERS; PTH/PTHRP