Pharmacokinetics of high-dose oral calcitriol: results from a phase 1 trial of calcitriol and paclitaxel

Clin Pharmacol Ther. 2002 Dec;72(6):648-59. doi: 10.1067/mcp.2002.129305.


Objectives: The data reported are from a trial designed to determine, in patients with advanced cancer, the maximum tolerated dose and pharmacokinetics of calcitriol when administered with paclitaxel, an agent whose antitumor activity in in vitro and in vivo studies has been shown to be enhanced by calcitriol. An additional goal was to evaluate the relationship between calcitriol dose and hypercalcemia.

Methods: Calcitriol was given orally for 3 consecutive days each week, and paclitaxel (80 mg/m(2)) was given intravenously weekly. Thirty-six patients were treated in cohorts composed of 3 to 9 patients, at escalating dose levels of calcitriol. The starting dose of calcitriol was 4 microg for 3 consecutive days each week, and the maximum dose administered was 38 microg for 3 consecutive days each week. The preparation of calcitriol used in this trial was a commercially available caplet (0.5 microg per caplet). Serum calcitriol concentrations were measured by radioimmunoassay. Detailed assessments of calcitriol pharmacokinetics were performed in 26 patients.

Results: There was substantial interpatient variation in peak serum calcitriol concentrations (C(max)), time to reach C(max), and area under the concentration versus time curve (AUC). Serum calcitriol AUC was not proportional to calcitriol dose (P =.0014). AUC for the 24-hour period after calcitriol administration [AUC (0-24)] at 38 microg was only 4 times that at 4 microg, instead of the 9.5-fold increase expected for a proportional relationship. Calcitriol plasma concentrations of 600 to 1440 pg/mL were achieved. No dose-limiting toxicity occurred in this trial.

Conclusions: Despite variability in absorption, very high doses of calcitriol can be safely administered with paclitaxel. The high calcitriol serum concentrations achieved in this study approach those that, both in vitro and in vivo, potentiate the cytotoxicity of taxanes and platinum analogs.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Area Under Curve
  • Calcitriol / administration & dosage
  • Calcitriol / blood
  • Calcitriol / pharmacokinetics*
  • Calcitriol / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Lung Neoplasms / drug therapy
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / therapeutic use
  • Prostatic Neoplasms / drug therapy
  • Radioimmunoassay


  • Antineoplastic Agents, Phytogenic
  • Calcitriol
  • Paclitaxel