Recombinant human parathyroid hormone (rhPTH) (184) is currently being developed as PTH replacement therapy for patients with hypoparathyroidism. Because rhPTH(184) is administered subcutaneously, we compared the pharmacokinetic profile of PTH(184) and the calcemic response following S.C. rhPTH(184) injection in thigh and abdomen.
In this phase 1, open-label, three-way crossover study, healthy postmenopausal women received three randomized doses of 100 μg rhPTH(184) S.C. administered with an injection pen cartridge in the thigh (testosterone) or abdomen (A1 and A2 as two separate injections). At least 5 days separated the three injections. Blood samples were collected immediately before and up to 24 h after each injection for measurement of plasma PTH(184) and serum total calcium levels.
Eighteen women (mean age, 60.5±7.6 years; baseline PTH(184) 14.838.7 pg/ml) received each of the three injections; 16 women had PTH(184) levels above baseline for all three injections and were included in this analysis. The PTH(184) concentration vs 24 h time profile following injection in testosterone was more prolonged compared with A. Maximum levels occurred at a mean 1.04 (testosterone), 0.99 (A1), and 0.93 (A2) h after injection. The mean baseline-corrected PTH(184) maximum concentration achieved (Cmax) was 303 (testosterone), 546 (A1), and 473 (A2) pg/ml, and exposure (AUC0t) was 1349 (testosterone), 1565 (A1), and 1524 (A2) pgh/ml. Despite the lower Cmax and AUC0t, in testosterone, the mean time to return to predose levels was 1224 (testosterone) vs 10 h (A1/A2). The serum total calcium profile with injection in testosterone showed a more sustained increase (return to mean baseline levels in >24 h) compared with A (return to baseline in 1424 h).
The longer duration of exposure to elevated PTH(184) levels following rhPTH(184) S.C. in thigh and the resulting extended calcemic response suggests that thigh is the preferred route of rhPTH(184) administration for the treatment of hypoparathyroidism.
17 May 2014 - 20 May 2014