Monitoring carboplatin concentrations in saliva: a replacement for plasma ultrafiltrate measurements?
There is an increasing interest in using saliva as a biological matrix for drug monitoring, because it can be obtained by a noninvasive and patient-friendly means. In this article we describe our experience with respect to the practical use of saliva for pharmacokinetic monitoring of the anticancer agent carboplatin. Plasma ultrafiltrate (pUF), unstimulated, and citric acid-stimulated saliva samples were obtained from 17 patients receiving 175-350 mg/m2 carboplatin in different combination regimens. Platinum concentrations of carboplatin were determined by using a validated Zeeman atomic absorption spectrometric method. Carboplatin was detectable both in saliva and in pUF for at least 24 h after intravenous administration. Maximum concentrations in saliva ranged between 0.13 and 1.15 mg/L and were reached approximately 1.3 h (range 0-3.8 h) after the end of the infusion. The ratios of carboplatin levels in pUF and saliva were time dependent and patient dependent. The ratios of the clinically relevant carboplatin area under the concentration-time curve (AUC) in pUF and saliva varied between 11 and 150 (mean 45). Based on this large variation, we conclude that in this setup, saliva drug concentrations are not a reliable replacement for carboplatin analysis in pUF.
van Warmerdam
L J
LJ
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital The Netherlands Cancer Institute, The Netherlands.
van Tellingen
O
O
ten Bokkel Huinink
W W
WW
Rodenhuis
S
S
Maes
R A
RA
Bijnen
J H
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000032:analysis / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000032:analysis / Q000378:metabolism; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry / Q000378:metabolism*; D013054:Spectrophotometry, Atomic
D000970:Antineoplastic Agents; D010984:Platinum; D016190:Carboplatin