title: Monocyte fructose 1,6-bisphosphatase and cytidine deaminase enzyme activities: potential pharmacodynamic measures of calcitriol effects in cancer patients.
abstract: OBJECTIVE
  To determine, in peripheral blood monocytes (PBM), whether the enzymatic activities of fructose 1,6-bisphosphatase (FBPase), cytidine deaminase (CDDase) and 24-hydroxylase (CYP24), enzymes regulated by calcitriol are useful pharmacodynamic (PD) measures of calcitriol effects in cancer patients.
  
  
  METHODS
  Cancer patients enrolled in a phase I clinical trial of calcitriol and carboplatin were studied. Baseline and calcitriol-induced changes in FBPase, CDDase and CYP24 activities were measured in PBM collected before, 6, 24, and 48 h after administration of calcitriol, prior to carboplatin, in doses ranging from 4 to 11 mug daily for 3 consecutive days (QDx3). Normal FBPase, CYP24 and CDDase activities were measured in PBM from untreated healthy volunteers.
  
  
  RESULTS
  Baseline activities in PBM from cancer patients and healthy volunteers were (median and range): 1.0 (0.0-43.5) and 4.4 (3.1- 8.2) nmol/min/mg protein for FBPase (P = 0.002); 2.5 (0.9-9.3) and 0.8 (0.4-2.0) fmol/h/10(6) cells for CYP24 (P = 0.016), and 5.6 (2.5-22.3) and 6.6 (1.1-47.4) nmol/min/mg protein for CDDase (P > 0.05), respectively. All calcitriol doses achieved peak serum calcitriol levels > x3 the physiological levels, increased cancer patient PBM FBPase activity to normal levels and decreased CDDase activity to undetectable levels within 48 h, with no significant change in CYP24 activity. These enzyme activity changes were not associated with hypercalcemia.
  
  
  CONCLUSIONS
  Calcitriol treatment-induced increase in FBPase and decrease in CDDase activities in cancer patient PBM are potential early and sensitive non-hypercalcemia PD measures of calcitriol effects.
authors: Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. josephia.muindi@roswellpark.org
authors: Josephia R
authors: JR
authors: Muindi
authors: Yibing
authors: Y
authors: Peng
authors: John W
authors: JW
authors: Wilson
authors: Candace S
authors: CS
authors: Johnson
authors: Robert A
authors: RA
authors: Branch
authors: Donald L
authors: DL
authors: Trump