Application of prolonged microdialysis sampling in carboplatin-treated cancer patients.
OBJECTIVE
To better understand the mechanisms underlying (in)sensitivity of tumors to anticancer drugs, assessing intra-tumor drug pharmacokinetics (PKs) could be important. We explored the feasibility of microdialysis in tumor tissue for multiple days in a clinical setting, using carboplatin as model drug.


METHODS
Plasma and microdialysate samples from tumor and adipose normal tissues were collected up to 47 h after dosing in eight carboplatin-treated patients with an accessible (sub)cutaneous tumor.


RESULTS
Pharmacokinetics were evaluable in tumor tissue in 6/8 patients and in adipose normal tissue in 3/8 patients. Concentration-time curves of unbound platinum in both the tissues followed the pattern of the curves in plasma, with exposure ratios of tissue versus plasma ranging from 0.64 to 1.46.


CONCLUSIONS
Microdialysis can be successfully employed in ambulant patients for multiple days, which enables one to study tissue PK of anticancer drugs in normal and malignant tissues in more detail.
Konings
Inge R H M
IR
Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands. i.konings@erasmusmc.nl
Engels
Frederike K
FK
Sleijfer
Stefan
S
Verweij
Jaap
J
Wiemer
Erik A C
EA
Loos
Walter J
WJ
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016190:Carboplatin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D016190:Carboplatin