Pharmacokinetics and tissue distribution of cisplatin and conjugates of cisplatin with carboxymethyldextran and A5B7 monoclonal antibody in CD1 mice

Journal of Pharmaceutical Sciences
D P McIntoshM Rowland

Abstract

The plasma disposition kinetics and tissue distribution of platinum was evaluated following intravenous bolus administration to CD1 immune-competent mice of cisplatin, cisplatin conjugated to anti-CEA monoclonal antibody A5B7 via a carboxymethyl dextran (CMdextran) carrier molecule, and cisplatin coupled to the CMdextran in the absence of antibody. In addition, the in vivo characteristics of 125I-labeled A5B7 were compared with and without conjugation to CMdextran. Conjugation of cisplatin [clearance (CL = 0.62 mL/min/g, volume of distribution at steady-state (Vdss) = 16 mL/g] to CMdextran restricted its tissue distribution (Vdss = 0.43 mL/g) and reduced its systemic clearance (CL = 0.055 mL/min/g). Subsequent conjugation of the complex to A5B7 further reduced both its distribution (Vdss = 0.20 mL/g) and clearance (CL = 0.016 mL/min/g). Clearance of A5B7 (CL = 0.002 mL/min/g) was increased by conjugation to CMdextran (CL = 0.014 mL/min/g); tissue distribution was unchanged. A5B7-CMdextran-cisplatin was relatively stable in plasma and other tissues, except the liver. The extent of distribution of platinum into tissues (lung, liver, muscle, kidney) was markedly influenced by conjugation, with the influence being greatest for unmo...Continue Reading

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Citations

May 22, 2003·Life Sciences·Elzíria A NunanTasso Moraes-Santos
Mar 17, 2001·International Journal of Biological Macromolecules·A A Tulub, V E Stefanov
Jun 30, 2012·International Journal of Nanomedicine·Hardeep S OberoiTatiana K Bronich
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Sep 26, 2006·Journal of Pharmaceutical Sciences·Wei WangSandeep Nema
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Mar 25, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Arong GaowaKoji Kawakami
Apr 23, 2014·Advanced Healthcare Materials·Thavasyappan ThambiJae Hyung Park
Jul 13, 2021·Chemical Communications : Chem Comm·Cinzia ImbertiPeter J Sadler
Aug 23, 2019·Journal of Inorganic Biochemistry·Virginia Del Solar, María Contel

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