The non linear relationship between calcitriol (1,25-D(3)) dose and AUC in cancer patients suggests that the commercially available caplet 1,25-D(3) formulation (Rocaltrol) cannot achieve the high systemic exposure associated with antitumor activity in animal models. The primary objective of this analysis was to determine whether a liquid 1,25-D(3) formulation had a more favorable pharmacokinetic profile. This analysis was based on the results obtained in 2 phase I clinical studies seeking to determine the maximum tolerated dose of 1,25-D(3) administered in combination with either dexamethasone or paclitaxel daily for three consecutive days weekly. Data were available for 12 patients treated with the caplet formulation at doses ranging from 12 microg to 21 microg, and for 16 patients treated with the liquid formulation at doses ranging from 13 microg to 36 microg; data for 19 patients were available at doses for which both formulations were used. There were no differences in C(max) and AUC(0-24 h) between the two formulations (P > 0.17) As was noted with the caplet formulation, dose-related proportional increases in C(max) and AUC(0-24 h) were not observed with liquid 1,25-D(3) at doses > or = 13 microg (P > 0.83). We conclude that the commercially available liquid 1,25-D(3) formulation offers no PK advantage over caplet formulation.