Analysis of microdialysates from cancer patients by capillary electrophoresis.
Microdialysis (MD) is an innovative clinical technique for measuring interstitial tissue pharmacokinetics and plasma-to-tissue transfer rates of drugs in humans. However, microdialysis requires the availability of specialized analytical techniques. Capillary electrophoresis (CE), which enables concentration measurements of small volume samples, theoretically constitutes an ideal analytical technique for measuring drug concentrations in microdialysates. In the present experiments, we aimed at assessing the potential utility and limitations of CE for analysis of microdialysates in a clinical situation. Microdialysates were obtained from primary breast cancer patients who received chemotherapy including 5-fluorouracil (5-FU; 600 mg/m2). Subsequently, 5-FU concentrations were measured in tumor - and subcutaneous adipose tissue - microdialysates by CE. By combining MD and CE, complete time versus concentrations profiles could be obtained for 5-FU in the interstitial tumor space and important clinical questions could be addressed. We conclude that the combination of MD and CE leads to important and previously inaccessible information about the drug distribution process in a clinical setting.
Mader
R M
RM
Department of Clinical Pharmacology, Vienna University School of Medicine, Austria.
Brunner
M
M
Rizovski
B
B
Mensik
C
C
Steger
G G
GG
Eichler
H G
HG
Müller
M
M
D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods*; D019075:Electrophoresis, Capillary; D005260:Female; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D017551:Microdialysis
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil