PHARMACOKINETICS AND BIOLOGIC EFFECTS OF CALCITRIOL IN NORMAL HUMANS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 105  (2) , 239-246
Abstract
The dose response and pharmacokinetics of orally administered calcitriol were investigated in normal humans. In 1 protocol, 6 volunteers received calcitriol 0.25 .mu.g twice a day, 0.5 .mu.g daily and 0.5 .mu.g twice a day, in successive weeks. Peak plasma levels of 1, 25(OH)2D [1, 25-dihydroxyvitamin O2] occurred 4-8 h after ingestion of a single dose of 0.5 .mu.g, with a return to baseline within 24 h. The 800 h calcitriol plasma levels were raised only when the drug was given twice daily. Urinary Ca excretion (UCa) was significantly increased from 199 .+-. 19 mg/24 h during the control period to similar levels of 302 .+-. 26 mg/24 h after 0.25 .mu.g twice a day and 284 .+-. 31 mg/24 h after 0.50 .mu.g daily. With 0.50 .mu.g twice a day, UCa was 417 .+-. 36 mg/24 hr, a value greater than after the lower doses (P < 0.05). In another protocol, 14 volunteers received calcitriol 0.25 .mu.g, 0.5 .mu.g and 1.0 .mu.g twice a day each for 14 days with interventing control periods of 2 wk. A dose-related response in urinary Ca/creatinine excretion occurred. UCa (mg Ca/mg creatinine) increased with calcitriol from 0.13 .+-. 0.014 mg to 0.15 .+-. 0.018 mg with 0.25 .mu.g twice a day, from 0.13 .+-. 0.010 mg to 0.22 .+-. 0.022 mg with 0.5 .mu.g twice a day and from 0.12 .+-. 0.012 mg to 0.23 .+-. 0.012 mg with 1 .mu.g twice a day (P < 0.05 with 0.25 .mu.g, P < 0.01 with 0.5 and 1 .mu.g twice a day). The maximum increase in UCa occurred sooner with 1 .mu.g twice a day than with 0.5 .mu.g. These changes in Ca excretion occurred with modest increments in serum calcitriol levels. Urinary hydroxyproline excretion did not increase, suggesting a dietary origin for the excreted Ca. The steady-state serum levels of calcitriol after 14 days of either 0.5 .mu.g or 1 .mu.g twice a day decayed toward basal levels with a half-life of 3.5 h. Treatment with calcitriol significantly suppressed the serum parathyroid hormone levels; as there was no hypercalcemia, changes in serum levels, nor urinary excretion of Mg, P or creatinine. Apparently, total dose rather than frequency of dosing determines the major biologic effects of calcitriol.