When CDDP is administered with sodium thiosulfate, the plasma filtered platinum (mixture of CDDP and mobile metabolites) concentration changes little, but the plasma CDDP concentration decreases dramatically, because CDDP binds strongly to sodium thiosulfate ( 8). When CDDP and sodium thiosulfate are administered concomitantly, the nephrotoxicity estimated by blood urea nitrogen (BUN) is ameliorated. In order to monitor the efficacy and safety of drug treatment, it is important to determine the concentration(s) of the active species.
The mobile metabolites in plasma are eliminated more slowly than that of CDDP and fixed metabolites are little decreased after CDDP and mobile metabolites have been eliminated ( 6, 7). The CDDP in plasma is instantly eliminated and mobile and fixed metabolites are gradually increased. The pharmacokinetic characteristics of these platinum species are different because their structures are different ( 6, 7). CDDP is biotransformed through binding to low molecular mass substances (such as glutathione, methionine and cysteine) and high molecular mass substances (such as albumin and nucleotides) and the resulting metabolites are called ‘mobile’ and ‘fixed’ metabolites, respectively ( 5). Aquated and unchanged CDDP also react readily with nucleophiles ( 3– 5). In biological fluids, CDDP is transformed immediately into aquated CDDP as a result of the release of chloride ion and equilibrium between CDDP and its aquated form is maintained. However, severe nephrotoxicity limits the dose and frequency of CDDP therapy ( 1).ĬDDP undergoes ligand-exchange reactions, which are virtually irreversible ( 2, 3). INTRODUCTIONĬisplatin (CDDP) is a potent anticancer drug used in the treatment of various types of cancer. Key words: population pharmacokinetic analysis – cisplatin – filtered platinum – total platinum Only the clearance of filtered platinum was significantly related to urinary N-acetyl-β- d-glucosaminidase and the other covariates were not related to these pharmacokinetic parameters with respect to unchanged cisplatin and total platinum concentrations.Ĭonclusion: The dosage regimen based on the filtered platinum concentration which is usually monitored may result in possible misinterpretation because the detected covariate is different between unchanged cisplatin and filtered platinum. Results: The clearance and volume of distribution for all platinum species studied were significantly related to the body surface area of the patients. Population pharmacokinetic analysis was performed using the program NONMEM (Version V) with the one- or two-compartment model with zero-order infusion. The concentrations of cisplatin and platinum in the plasma were determined by high-performance liquid chromatography and atomic absorption spectrometry, respectively. Blood samples were taken at about three points per patient. Methods: Twenty-seven patients (23 males, four females) were administered cisplatin (60–100 mg/m 2) with intravenous constant infusion for 90 min. In this work, we studied population pharmacokinetic analysis based on these platinum concentrations.
However, these concentrations represent a mixture of unchanged cisplatin and metabolites. Background: Usually, total and filtered platinum concentrations in plasma are monitored after cisplatin administration.
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