Summary
The ability of TNO6 to react with human plasma was investigated by in vitro incubation of plasma or plasma fractions with injectable TNO6. HPLC, ultrafiltration and flameless atomic absorption spectrophotometry were used to separate the platinum-containing chemical species and to measure the platinum content. The initial concentration of TNO6 in plasma declines very rapidly. The kinetics of the loss of initial TNO6 is very different from that of cisplatin loss. Most of the TNO6 is bound more quickly to proteins, while a little is transformed to less reactive or nonreactive platinum species. The level of final nonreactive platinum species depends on the particular plasma concerned. In addition, the reactivity of TNO6 towards proteins is very sensitive to Cl- concentration. The usefulness of HPLC for the study of TNO6 kinetics is demonstrated.
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References
Gullo JJ, Litterst CL, McGuire PJ, Sikic BI, Hoth DF, Woolley PV (1980) Pharmacokinetics and protein binding of CDDP administered as a one-hour or as a twenty-hour infusion. Cancer Chem Pharmacol 5:21–26
Le Roy AF, Lutz RJ, Dedrick RL, Litterst CL, Guarino AM (1979) Pharmacokinetic study of CDDP in the beagle dog: thermodynamic and kinetic behavior of DDP in a biological milieu. Cancer Treat Rep 63:59–71
Long DF, Repta AJ (1981) Cisplatin: chemistry, distribution and biotransformation. Biopharm Drug Dispos 2:1–16
Prestayko AW (1981a) Molecular pharmacology of cisplatin: In: Cancer and chemotherapy, vol 3. Academic Press, New York, pp 303–310
Prestayko AW (1981b) Clinical pharmacology of cisplatin: In: Cancer and chemotherapy, vol 3. Academic Press, New York, pp 351–357
Prestayko AW, Crooke ST, Carter SK (eds) (1980) Cisplatin: Current status and new developments. Academic Press, New York
Repta AJ, Long DF (1980) Reactions of cisplatin with human plasma and plasma fractions: In: Prestayko AW, Crooke ST, Carter SK (eds) Cisplatin: Current status and new developments. Academic Press, New York, pp 285–304
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Hecquet, B., Adenis, L. & Demaille, A. In vitro interactions of TNO6 with human plasma. Cancer Chemother. Pharmacol. 11, 177–181 (1983). https://doi.org/10.1007/BF00254200
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DOI: https://doi.org/10.1007/BF00254200