Doxorubicin and 5-fluorouracil plasma concentrations and detectability in parotid saliva

Abstract

Doxorubicin and 5-fluorouracil pharmacokinetics were studied in 19 volunteers with various advanced neoplastic diseases who received 50-90 mg doxorubicin or 600-1000 mg 5-fluorouracil intravenously, followed by plasma and parotid saliva collection over a 75 min period. The extent to which these chemotherapeutic agents are bound to plasma proteins, at concentrations chosen to approximate plasma concentrations, was measured by equilibrium dialysis. Both agents were quantitated by high-performance liquid chromatography. As reported previously, a wide range of plasma levels were found among patients receiving similar doses of either doxorubicin or 5-fluorouracil. It appears that in addition to being quickly cleared from the plasma both chemotherapeutic agents are excreted in detectable amounts in parotid saliva, a route of elimination heretofore given little or no attention. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to 5-fluorouracil after intravenous administration and may play a part in causing stomatitis in patients receiving it by this route. Since there are huge interindividual and pronounced intraindividual differences in S/P ratios mostly not systematically related to the drugs' concentration in plasma, the concentration in parotid saliva was not useful in predicting the level of free doxorubicin or 5-fluorouracil in plasma.

Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells

“…24 Carboplatin and doxorubicin were also tested, with concentrations of 50 and 1mmol/L, respectively, being representative of patient serum levels. 25,26 Previous publications from our laboratory have demonstrated that the loss of cell viability in this assay corresponds to ovarian cancer cell apoptosis. 20,21 Figures 2 and 3 demonstrate that the reduction in cell viability with chemotherapies tested in A2780 and SKOV3 is enhanced when cells were preexposed to metformin for 24 hours.…”

CE‐LIF method for the separation of anthracyclines: Application to protein binding analysis in plasma using ultrafiltration

“…Ultrafiltration was previously applied to the serum protein binding of these anthracyclines, binding values in the range of 56.9 -63.1% were obtained [15]. The protein binding results achieved in this study were also equivalent to those previously obtained by equilibrium dialysis [10,13,14]. As anthracyclines are highly protein bound, the volume of bound drug will be reduced.…”

“…In another application of equilibrium dialysis, the protein binding of DOX in both human and rat plasma was also determined using HPLC. The extent to which DOX was bound to rat plasma was determined to be 78% [10,13]. In addition, using ultrafiltration in conjunction with HPLC the serum protein binding of DAN, DOX and EPI was determined and the degree of binding was reported to vary in the range of 61 -78.4% [15].…”

Development and validation of a liquid chromatographic method for the simultaneous determination of four anthracyclines and their respective 13-S-dihydro metabolites in plasma and saliva

“…Celio et al [26] and Bressolle et al [27] reported salivary concentrations of DOX, but only Dodde et al [22] presented a validated assay for EPI and EPIol. However, saliva is a promising matrix to predict gastrointestinal side effects (e.g.…”