Pharmacokinetics of 5-fluorouracil and cyclophosphamide in depression rats.
OBJECTIVE
Efficacy and toxicity of the drug are mainly determined by physicochemical properties and pharmacological effects of its own. In addition, they are also affected by other factors, such as gender, age, genetic character, pathophysiological status, mood states and so on. The paper aims to study whether mood disorder alters drug metabolism process through the pharmacokinetic research on some clinically important anticancer drugs in depression model rats.


METHODS
The depression model rats were built by exposing to chronic unpredicted mild stresses (CUMS) for 8 weeks. 36 female Sprague-Dawley (SD) rats were randomized into model group and control group. In each group, 18 rats were randomized into 2 subgroups: 5-fluorouracil (5-FU) subgroup and cyclophosphamide (CP) subgroup which were given a certain doses of 5-FU and CP. The blood samples were collected at different time points and plasma drug concentration were respectively assayed by high performance liquid chromatography (HPLC) for 5-FU and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for CP. Pharmacokinetic parameters were processed with DAS software.


RESULTS
There were significant differences in the pharmacokinetic parameters of 5-FU and CP between in depression model rats group and in the normal control group (p < 0.05), except t1/2alpha (p > 0.05) for CP pharmacokinetics in depression model rats group and in the normal control rats group, with the value of those was 0.07 and 0.09 h.


CONCLUSIONS
Depression mood disorder might alter drug metabolism process.
Department of Clinical Pharmacology, Fengxian Central Hospital, Shanghai, China.
J J
JJ
Duan
T
T
Zhou
X
X
Chen
Y
Y
Wang
Y G
YG
Wen
F
F
Xu
D000339:Affect; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001522:Behavior, Animal; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003863:Depression / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000201:enzymology; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000150:complications; D053719:Tandem Mass Spectrometry
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D012701:Serotonin; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D005472:Fluorouracil