Abstract
Plasma ultrafiltrates are routinely used in pharmacokinetic studies of carboplatin. Experiments were performed to detect and quantitate artifactual decreases in the platinum concentration of ultrafiltrates prepared from plasma samples stored at −20°C and −70°C. Carboplatin was added to anticoagulated, whole human blood to produce a 20 μg/ml concentration. Plasma produced from the blood was stored frozen at either −20°C or −70°C. Aliquots from each storage condition were thawed and ultrafiltered once a week for up to 100 days. Platinum concentrations in ultrafiltrates and plasma were determined by flameless atomic absorption spectrometry. There was no loss of ultrafilterable platinum in plasma samples stored at −70°C, whereas there was a steady decrease in free platinum concentration in ultrafiltrates prepared from plasma samples stored at −20°C. These results imply that pharmacokinetic studies of carboplatin should use ultrafiltrates prepared immediately or that plasma for such studies should be stored at −70°C. Storage of carboplatincontaining plasma at −20°C and subsequent ultrafiltration is not acceptable, because measurement of platinum in such ultrafiltrates will be artifactually low.
References
Bunn PA Jr, Canetta R, Ozols RF, Rozencweig M (eds) (1990) Carboplatin (JM-8). Saunders, Philadelphia
D'Argenio DZ, Schumitzky A (1979) A program package for simulation and parameter estimation in pharmacokinetic systems. Comput Methods Programs Biomed 9: 115
DeConti RC, Toftness BR, Lange RC, Creasey WA (1973) Clinical and pharmacological studies withcis-diamminedichloroplatinum (II). Cancer Res 33: 3310
Egorin MJ, Van Echo DA, Olman EA, Whitacre MY, Forrest A (1985) Prospective validation of pharmacologically based dosing scheme for the cisplatin analog, carboplatin. Cancer Res 45: 6502
Egorin MJ, Van Echo DA, Tipping SJ, Olman EA, Whitacre MY, Thompson BW, Aisner J (1984) Pharmacokinetics and dosage reduction of carboplatin in patients with impaired renal function. Cancer Res 44: 5432
Gaver RC, George AM, Deeb G (1987) In vitro stability, plasma protein binding and blood cell partitioning of14C-carboplatin. Cancer Chemother Pharmacol 20: 271
Ghazal-Aswad S, Newell DR, Calvert AH (1991) A single sample assay for the calculation of the area under the free carboplatin plasma concentration v. time curve. Br J Cancer 63: 7
Gonias SL, Pizzo SV (1983) Complexes of serum albumin andcis-dichlorodiammineplatinum (II). J Biol Chem 258: 5764
Gormley PE, Bull JM, Leory AF, Cysyk R (1979) Kinetics ofcis-dichlorodiammineplatinum. Clin Pharmacol Ther 25: 351
Jodrell DI, Egorin MJ, Canetta RM, Langenberg P, Goldbloom EP, Burroughs JN, Goodlow JL, Tan S, Wiltshaw E (1992) Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. J Clin Oncol 10: 520
Laznickova A, Laznicek M, Kvetina J, Drobnik J (1986) Pharmacokinetics and plasma protein binding of two platinum cytostatics CHIP and CBDCA in rats. Cancer Chemother Pharmacol 17: 133
Leroy AF, Thompson WC (1989) Binding kinetics of tetrachloro-1,2-diaminocyclohexaneplatinum (IV) (tetraplatin) andcis-diamminedichloroplatinum (II) at 37 degrees C with human plasma proteins and with bovine serum albumin. Does aquation precede protein binding? J Natl Cancer Inst 31: 427
Leroy AF, Lutz RJ, Dedrick RL, Litterst CL, Guarino AM (1979) Pharmacokinetic study ofcis-dichlorodiammineplatinum (II) (DDP) in the beagle dog: Thermodynamic and kinetic behavior of DDP in a biologic milieu. Cancer Treat Rep 63: 59
Litterst CL, Gram TE, Dedrick RL, Leroy AF, Guarino AM (1976) Distribution and disposition of platinum following intravenous administration ofcis-diamminedichloroplatinum (II). Cancer Res 36: 2340
Perera A, Jackson H, Sharma HL, McAuliffe CA, Fox BW (1992) A comparative binding of platinum anti-tumour compounds to plasma proteins in the rat (in vivo) and mouse (in vitro). Chem Biol Interact 35: 133
Reed E, Kohn KW (1990) Platinum analogues. In: Chabner BA, Collins JM (eds) Cancer chemotherapy: principles and practice. Lippincott, Philadelphia, p 465
Reyno LM, Egorin MJ, Canetta RM, Jodrell DI, Swenerton KD, Pater JL, Burroughs JN, Novak MJ, Sridhara R (1993) Impact of cyclophosphamide on relationships between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer. J Clin Oncol 11: 1156
Sorensen BT, Stromgren A, Jakobsen P, Jakobsen A (1993) A limited sampling method for estimation of the carboplatin area under the curve. Cancer Chemother Pharmacol 31: 324
Tosetti F, Rocco M, Fulco RA, Chiara S, Bruzzone M, Campora E, Esposito M (1988) Serial determination of platinum, protein content and free sulfhydryl levels in plasma of patients treated with cisplatin or carboplatin. Anticancer Res 3: 381
Vijgh WJF van der, Klein I (1986) Protein binding of five platinum compounds. Comparison of two ultrafiltration systems. Cancer Chemother Pharmacol 18: 123
Vijgh WIF van der (1991) Clinical pharmacokinetics of carboplatin. Clin Pharmacokinet 21: 242
Yarbro JW, Bornstein RS, Mastrangelo MJ (eds) (1992) Carboplatin (JM-8) update: current perspectives and future directions. Semin Oncol, [Suppl 2]: 19 (1)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Erkmen, K., Egorin, M.J., Reyno, L.M. et al. Effects of storage on the binding of carboplatin to plasma proteins. Cancer Chemother. Pharmacol. 35, 254–256 (1995). https://doi.org/10.1007/BF00686557
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00686557