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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 1/2007

01-01-2007 | Original Article

Monocyte fructose 1,6-bisphosphatase and cytidine deaminase enzyme activities: potential pharmacodynamic measures of calcitriol effects in cancer patients

Authors: Josephia R. Muindi, Yibing Peng, John W. Wilson, Candace S. Johnson, Robert A. Branch, Donald L. Trump

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2007

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Abstract

Purpose: 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 μg daily for 3 consecutive days (QD×3). 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/106 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 > ×3 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.
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Metadata
Title
Monocyte fructose 1,6-bisphosphatase and cytidine deaminase enzyme activities: potential pharmacodynamic measures of calcitriol effects in cancer patients
Authors
Josephia R. Muindi
Yibing Peng
John W. Wilson
Candace S. Johnson
Robert A. Branch
Donald L. Trump
Publication date
01-01-2007
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2007
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-006-0247-0

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