Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics of Carboplatin

  • Review Article
  • Drug Disposition
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Carboplatin [diammine(1,1-cyclobutanedicarboxylato)platinum(II)] is one of the most promising second generation platinum compounds. Its greater chemical stability in comparison with cisplatin accounts for its lower reactivity with nucleophilic sites of DNA, and may therefore be related to the higher dose necessary to obtain an antitumour effect similar to that of cisplatin. The lower reactivity with proteins may be related to the observed reduction in nephrotoxicity. Its dose-limiting toxicity is myelosuppression, especially thrombocytopenia.

Total and ultrafilterable platinum are detected by flameless atomic absorption spectrophotometry, and high performance liquid chromatography with either UV or electrochemical detection is used for the quantification of carboplatin. These 3 species have been measured as a function of time in biological fluids and tissues to determine their pharmacokinetics.

Carboplatin has high stability in infusion fluids in the absence of chloride, but it is less stable in plasma and urine. Protein binding is limited, while the low uptake in red blood cells appears to be species dependent.

Commonly, carboplatin is administered intravenously, and its pharmacokinetics are linear up to a dose of 2400 mg/m2. In comparison with cisplatin, carboplatin has longer half-lives of ultrafilterable platinum (23 and 120 min versus 6 and 36 min for distribution and initial elimination half-lives, respectively) and a higher cumulative urinary platinum excretion (77 versus 28% of the dose in 24h), both due to the lower protein binding of carboplatin. The terminal half-life of total platinum is comparable between the 2 compounds (5.8 versus 5.4 days). This value most probably represents the breakdown of proteins to which both compounds are irreversibly bound.

Relationships between pharmacokinetics (area under the curve) and pharmacodynamics (extent of myelosuppression or extent of existing kidney failure) have allowed the development of equations for rational dosage reduction. Intraperitoneal administration has been used in cases of residual ovarian cancer: as a result of its higher hydrophilicity and higher molecular weight, carboplatin is cleared more slowly from the peritoneal cavity than cisplatin (6 vs 15 ml/min). The low bioavailability (4 to 12%) and the gastrointestinal side effects observed did not warrant further studies with oral administration.

In contrast to results from animal studies, the modulation of carboplatin-induced myelo-suppression by diethyldithiocarbamate (DDTC) was not clinically successful. Valuable alternatives may be the combination with WR2721 or colony-stimulating factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bannister SJ, Sternson LA, Repta AJ. Evaluation of reductive amperometric detection in the liquid chromatographic determination of antineoplastic platinum complexes. Journal of Chromatography 273: 301–318, 1983

    Article  PubMed  CAS  Google Scholar 

  • Belani CP, Egorin MJ, Abrams JS, Hiponia D, Eisenberger M, et al. A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide. Journal of Clinical Oncology 7: 1896–1902, 1989

    PubMed  CAS  Google Scholar 

  • Binks SP, Dobrota M. Kinetics and mechanism of uptake of platinum-based pharmaceuticals by the rat small intestine. Biochemical Pharmacology 40: 1329–1336, 1990

    Article  PubMed  CAS  Google Scholar 

  • Borch RF, Dedon PC, Gringeri A, Montine TJ. Inhibition of platinum drug toxicity by diethyldithiocarbamate. In Nicolini (Ed.) Platinum and other metal coordination compounds in cancer chemotherapy, pp. 216–227, Martinus Nijhoff Publishing, Boston, 1988

    Chapter  Google Scholar 

  • Boughattas NA, Lévi, Hecquet B, Lemaigre G, Roulon A, Fournier C, Reinberg A. Toxicities and tissue pharmacokinetics of oxaliplatin and carboplatin depend upon their dosing time in mice. Annual Review of Chronopharmacology 5: 351–354, 1988

    CAS  Google Scholar 

  • Boven E, Van der Vijgh WJF, Nauta MM, Schlüper HMM, Pinedo HM. Comparative activity and distribution studies of five platinum analogues in nude mice bearing human ovarian carcinoma xenografts. Cancer Research 45: 86–90, 1985

    PubMed  CAS  Google Scholar 

  • Calvert AH, Harland SJ, Newell DR, Siddik ZH, Harrap KR. Phase I studies with carboplatin at the Royal Marsden Hospital. Cancer Treatment Reviews 12 (Suppl. A): 51–57, 1985

    Article  PubMed  Google Scholar 

  • Calvert AH, Harland SJ, Newell DR, Siddik ZH, Jones AC, et al. Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II. Cancer Chemotherapy and Pharmacology 9: 140–147, 1982

    Article  PubMed  CAS  Google Scholar 

  • Calvert AH, Newell DR, Gumbrell LA, O’Reilly S, Burneil M, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. Journal of Clinical Oncology 7: 1748–1756, 1989

    PubMed  CAS  Google Scholar 

  • Canetta R, Bragman K, Smaldone L, Rozencweig M. Carboplatin: current status and future prospects. Cancer Treatment Reviews 15 (Suppl. B): 17–32, 1988

    Article  PubMed  Google Scholar 

  • Cheung Y-W, Cradock JC, Vishnuvajjala BR, Flora KP. Stability of cisplatin, iproplatin, carboplatin and tetraplatin in commonly used intravenous solutions. American Journal of Hospital Pharmacy 44: 124–130, 1987

    PubMed  CAS  Google Scholar 

  • Cleare MJ, Hydes PC, Hepburn DR, Malerbi BW. Antitumor platinum complexes: structure-activity relationships. In Prestayko et al. (Eds) Cisplatin, current status and new developments, pp. 149–170, Academic Press, New York, 1980

    Google Scholar 

  • Curt GA, Grygiel JJ, Corden BJ, Ozols RF, Weiss RB, et al. A phase I and pharmacokinetic study of diamminecyclobutanedicarboxylatoplatinum (NSC 241240). Cancer Research 43: 4470–4473, 1983

    PubMed  CAS  Google Scholar 

  • Daley-Yates PT. The metabolites of platinum antitumour drugs and their biological significance. In McBrien & Slater (Eds) Biomedical mechanisms of platinum antitumour drugs, pp. 121–137, IRL Press Limited, Oxford, 1986

    Google Scholar 

  • Dedon PC, Borch RF. Characterization of the reactions of platinum antitumor agents with biologic and nonbiologic sulfur-containing nucleophiles. Biochemical Pharmacology 36: 1955–1964, 1987

    Article  PubMed  CAS  Google Scholar 

  • DeGregorio MW, Lum BL, Holleran WM, Wilbur BJ, Sikic BI. Preliminary observations of intraperitoneal carboplatin pharmacokinetics during a phase I study of the Northern California Oncology Group. Cancer Chemotherapy and Pharmacology 18: 235–238, 1986

    Article  PubMed  CAS  Google Scholar 

  • DeNeve W, Valeriote F, Tapazoglou E, Everett C, Khatana A, et al. Discrepancy between cytotoxicity and DNA interstrand crosslinking of carboplatin and cisplatin in vivo. Investigational New Drugs 8: 17–24, 1990

    Article  PubMed  CAS  Google Scholar 

  • Dible SE, Siddik ZH, Boxall FE, Harrap KR. The effect of diethyldithiocarbamate on the haematological toxicity and antitumour activity of carboplatin. European Journal of Cancer and Clinical Oncology 23: 813–818, 1987

    Article  CAS  Google Scholar 

  • Dible SE, Siddik ZH, Harrap KR. The comparative tissues distribution of platinum and 14C in mice receiving 14C-labelled carboplatin. Cancer Chemotherapy and Pharmacology 22: 11–16, 1988

    Article  PubMed  CAS  Google Scholar 

  • Douple EB, Totten MD, Spencer F. Platinum levels in murine tumor following intraperitoneal administration of cisplatin or paraplatin. NCI Monograms 6: 129–132, 1988

    Google Scholar 

  • Duncan GF, Faulkner III HC, Farmen RH, Pittman KA. Liquid chromatographic procedure for the quantitative analysis of carboplatin in beagle dog plasma ultrafiltrate. Journal of Pharmaceutical Sciences 77: 273–276, 1988

    Article  PubMed  CAS  Google Scholar 

  • Egorin MJ, Forrest A. Pharmacokinetics and dosage reduction of cis-diammine (1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function. Cancer Research 47: 3606–3607, 1987

    Google Scholar 

  • Egorin MJ, Van Echo DA, Olman EA, Whitacre MY, Forrest A, et al. Prospective validation of a pharmacologically based dosing scheme for the cis-diamminedichloroplatinum(II) analogue diamminecyclobutanedicarboxylatoplatinum. Cancer Research 45: 6502–6506, 1985

    PubMed  CAS  Google Scholar 

  • Egorin MJ, Van Echo DA, Tipping SJ, Olman EA, Whitacre MY, et al. Pharmacokinetics and dosage reduction of cis-diammine(1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function. Cancer Research 44: 5432–5438, 1984

    PubMed  CAS  Google Scholar 

  • Elferink F, Leeuwenkamp OR, Pinedo HM, Van der Vijgh WJF. Electrochemistry of platinum complexes I: Polarographic reduction mechanism with reference to electrochemical detection. Journal of Electroanalytical Chemistry 238: 297–313, 1987a

    Article  CAS  Google Scholar 

  • Elferink F, Van der Vijgh WJF, Klein I, Pinedo HM. Interaction of cisplatin and carboplatin with sodium thiosulfate: reaction rates and protein binding. Clinical Chemistry 32: 641–645, 1986b

    PubMed  CAS  Google Scholar 

  • Elferink F, Van der Vijgh WJF, Klein I, Ten Bokkel Huinink WW, Dubbelman R, et al. Pharmacokinetics of carboplatin after intraperitoneal administration. Cancer Chemotherapy and Pharmacology 21: 57–60, 1988

    Article  PubMed  CAS  Google Scholar 

  • Elferink F, Van der Vijgh WJF, Klein I, Vermorken JB, Gall HE, et al. Pharmacokinetics of carboplatin after iv administration. Cancer Treatment Reports 71: 1231–1237, 1987b

    PubMed  CAS  Google Scholar 

  • Elferink F, Van der Vijgh WJF, Pinedo HM. On-line differential pulse Polarographic detection of carboplatin in biological samples after chromatographic separation. Analytical Chemistry 58: 2293–2296, 1986a

    Article  PubMed  CAS  Google Scholar 

  • Elferink F, Van der Vijgh WJF, Ten Bokkel Huinink WW, Vermorken JB, Klein I, et al. Pharmacokinetics of ethylenediamminemalonatoplatinum (II) (JM-40) during phase I trials. British Journal of Cancer 56: 479–483, 1987

    Article  PubMed  CAS  Google Scholar 

  • El-Yazigi A, Amer M, Martin CR. Pharmacokinetics of platinum in cancer patients treated with carboplatin in combination with high-dose methotrexate. Pharmaceutical Research 6: 492–496, 1989

    Article  PubMed  CAS  Google Scholar 

  • Ewen C, Perera A, Hendry JH, McAuliffe CA, Sharma H, et al. An autoradiographic study of the intrarenal localisation and retention of cisplatin, iproplatin and paraplatin. Cancer Chemotherapy and Pharmacology 22: 241–245, 1988

    Article  PubMed  CAS  Google Scholar 

  • Fichtinger-Schepman AMJ, Van der Velde-Visser SD, Van Dijk-Knijnenburg HCM, Van Oosterom AT, Baan RA, et al. Kinetics of the formation and removal of cisplatin-DNA adducts in blood cells and tumor tissue of cancer patients receiving chemotherapy; comparison with in vitro adduct formation. Cancer Research 50: 7887–7894, 1990

    PubMed  CAS  Google Scholar 

  • Fichtinger-Schepman AMJ, Van Oosterom AT, Lohman PHM, Berends F. Interindividual human variation in cisplatinum sensitivity, predictable in an in vitro assay? Mutation Research 190: 59–62, 1987

    PubMed  CAS  Google Scholar 

  • Fichtinger-Schepman AMJ, Vendrik CPJ, Van Dijk-Knijnenburg CM, De Jong WH, Van der Minnen ACE, et al. Platinum concentrations and DNA adduct levels in tumors and organs of cisplatin-treated LOU/M rats inoculated with cisplatin-sensitive or -resistant immunoglobulin M immunocytoma. Cancer Research 49: 2862–2867, 1989

    PubMed  CAS  Google Scholar 

  • Fish RG, Shelley MD, Griffiths H, Adams M. Pharmacokinetics and dosage reduction of cis-diammine(1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function. Cancer Research 47: 3606–3607, 1987

    PubMed  CAS  Google Scholar 

  • Gaver RC, Colombo N, Green MD, George AM, Deeb G, et al. The disposition of carboplatin in ovarian cancer patients. Cancer Chemotherapy and Pharmacology 22: 263–270, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Gaver RC, Deeb G. High-performance liquid chromatographic procedures for the analysis of carboplatin in human plasma and urine. Cancer Chemotherapy and Pharmacology 16: 201–206, 1986

    Article  PubMed  CAS  Google Scholar 

  • Gaver RC, George AM, Deeb G. In vitro stability, plasma protein binding and blood cell partitioning of 14C-carboplatin. Cancer Chemotherapy and Pharmacology 20: 271–276, 1987

    Article  PubMed  CAS  Google Scholar 

  • Gaver RC, George AM, Duncan GF, Morris AD, Deeb G, et al. The disposition of carboplatin in the beagle dog. Cancer Chemotherapy and Pharmacology 21: 197–202, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Goel R, Cleary SM, Horton CA, Kirmani S, Abramson I, et al. Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin. Journal of the National Cancer Institute 81: 1552–1560, 1989

    Article  PubMed  CAS  Google Scholar 

  • Gooyer C, Veltkamp AC, Baumann RA, Veithorst NH, Frei RW, et al. Analysis of platinum complexes by liquid chromatography with quenched phosphorescence detection. Journal of Chromatography 312: 337–344, 1984

    Article  Google Scholar 

  • Gringeri A, Keng PC, Borch RF. Diethyldithiocarbamate inhibition of murine bone marrow toxicity caused by cisdiamminedichloroplatinum(II) or diammine(1,1-cyclobutanedicarboxylato)platinum(II). Cancer Research 48: 5708–5712, 1988

    PubMed  CAS  Google Scholar 

  • Harland SJ, Newell DR, Siddik ZH, Chadwick R, Calvert AH, et al. Pharmacokinetics of cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) in patients with normal and impaired renal function. Cancer Research 44: 1693–1697, 1984

    PubMed  CAS  Google Scholar 

  • Harrap KR, Jones M, Siracky J, Pollard LA, Kelland LR. The establishment, characterization and calibration of human ovarian carcinoma xenografts for the evaluation of novel platinum anticancer drugs. Annals of Oncology 1: 65–76, 1990

    PubMed  CAS  Google Scholar 

  • Hecquet B, Caty A, Fournier C, Lefebvre JL, Adenis L. Comparison of platinum concentrations in human head and neck tumours following administration of carboplatin, iproplatin or cisplatin. Bulletin du Cancer 74: 433–436, 1987

    PubMed  CAS  Google Scholar 

  • Hecquet B, Leroy A, Lefebvre JL, Peyrat JP, Adenis L. Uptake of platinum compounds in human tumors. In vitro study. Bulletin du Cancer 73: 535–541, 1986

    PubMed  CAS  Google Scholar 

  • Hopfer SM, Ziebka L, Sunderman FW, Sporn JR, Greenberg BR. Direct analysis of platinum in plasma and urine by electrothermal atomic absorption spectrophotometry. Annals of Clinical and Laboratory Science 19: 389–396, 1989

    PubMed  CAS  Google Scholar 

  • Kauffmann J-M, Patriarche GJ, Mebsout F. Electrochemical behaviour of platinum(II) antitumour drugs at platinum and carbon paste electrodes. In Smyth & Vos (Eds) Electrochemistry, sensors and analysis, pp. 367–377, Elsevier Science Publishers BV, Amsterdam, 1986

    Google Scholar 

  • Knox RJ, Friedlos F, Lydall DA, Roberts JJ. Mechanism of cytotoxicity of anticancer platinum drugs: evidence that cis-diamminedichloroplatinum(II) and cis-diammine(1,1-cyclobutanedicarboxylato) platinum (II) differ only in the kinetics of their interaction with DNA. Cancer Research 46: 1972–1979, 1986

    PubMed  CAS  Google Scholar 

  • Kodier JM, Trump DL, Tutsch KD, Earhart RH, Davis TE, et al. Phase I clinical trial and pharmacokinetics of carboplatin (NSC 241240) by single monthly 30-minute infusion. Cancer 57: 222–225, 1986

    Article  Google Scholar 

  • Krull IS, Ding X-D, Braverman S, Selavka C. Trace analysis for cis-platinum anti-cancer drugs via LCEC. Journal of Chromatographic Science 21: 166–173, 1983

    PubMed  CAS  Google Scholar 

  • Lee EJ, Egorin MJ, Van Echo DA, Cohen AE, Tait N, et al. Phase I and pharmacokinetic trial of carboplatin in refractory adult leukemia. Journal of the National Cancer Institute 80: 131–135, 1988

    Article  PubMed  CAS  Google Scholar 

  • Leyland-Jones B. Whither the modulation of platinum? Journal of the National Cancer Institute 80: 1432–1433, 1988

    Article  PubMed  CAS  Google Scholar 

  • Litterst CL. Plasma pharmacokinetics, urinary excretion and tissue distribution of platinum following IV administration of cyclobutanedicarboxylatoplatinum-II and cis-platinum to rabbits. In Hacker et al. (Eds) Platinum coordination complexes in cancer chemotherapy, pp. 71–81, Martinus Nijhoff Publishing, Boston, 1984

    Chapter  Google Scholar 

  • Los G, Mutsaers PHA, Dubbelman R, Van der Hoeven CJ, McVie JG. Platinum distribution in rat and human peritoneal autopsy tumor samples after treatment with cDDP and CBDCA. Proceedings of the NCI-EORTC Symposium 6. Abstract no. 220, 1989

  • Los G, Nagel JD, McVie JG. Anti-tumor effect of cisplatin, carboplatin, mitoxantrone and doxorubicin on peritoneal tumor growth after intraperitoneal and intravenous chemotherapy: a comparative study. Selective Cancer Therapeutics 6: 73–82, 1990

    Article  PubMed  CAS  Google Scholar 

  • Los G, Verdegaal EME, Mutsaers PHA, McVie JG. Penetration of carboplatin and cisplatin into rat peritoneal tumor nodules after intraperitoneal chemotherapy: a comparative study. Cancer Chemotherapy and Pharmacology, in press, 1991

  • Markman M, Hakes T, Reichman B, Hoskins W, Rubin S, et al. Intraperitoneal therapy in the management of ovarian carcinoma. Yale Journal of Biology and Medicine 62: 393–403, 1989

    PubMed  CAS  Google Scholar 

  • Marsh KC, Sternson LA, Repta AJ. Post-column reaction detector for platinum(II) antineoplastic agents. Analytical Chemistry 56: 491–497, 1984

    Article  PubMed  CAS  Google Scholar 

  • McGuire WP, Abeloff MD. Carboplatin substitution for cisplatin in the treatment of ovarian carcinoma — a word of caution. Journal of the National Cancer Institute 81: 1438–1439, 1989

    Article  PubMed  CAS  Google Scholar 

  • McVie JG. Intraperitoneal chemotherapy experience in the Netherlands Cancer Institute. British Journal of Cancer 56: 702–703, 1987

    Google Scholar 

  • McVie JG, Ten Bokkel Huinink W, Dubbelman R, Franklin H, Van der Vijgh WJF, et al. Phase I study and pharmacokinetics of intraperitoneal carboplatin. Cancer Treatment Reviews 12 (Suppl. A): 35–41, 1985

    Article  PubMed  Google Scholar 

  • Micetich KC, Barnes D, Erickson LC. A comparative study of the cytotoxicity and DNA-damaging effects of cis-(diammino(1,1-cyclobutanedicarboxylato)-platinum(II) and cis-diamminedichloroplatinum(II) on L1210 cells. Cancer Research 45: 4043–4047, 1985

    PubMed  CAS  Google Scholar 

  • Momburg R, Bourdeaux M, Sarrazin M, Roux F, Briand C. In vitro plasma binding of some second generation antitumor platinum complexes. European Journal of Drug Metabolism and Pharmacokinetics 10: 77–83, 1985

    Article  PubMed  CAS  Google Scholar 

  • Motzer RJ, Niedzwiecki D, Isaacs M, Menendez-Botet C, Tong WP, et al. Carboplatin-based chemotherapy with pharmacokinetic analysis for patients with hemodialysis-dependent renal insufficiency. Cancer Chemotherapy and Pharmacology 27: 234–238, 1990

    Article  PubMed  CAS  Google Scholar 

  • Muggia FM. Overview of carboplatin: replacing, complementing and extending the therapeutic horizons of cisplatin. Seminars in Oncology 16: 7–13, 1989

    PubMed  CAS  Google Scholar 

  • Mulder POM, De Vries EGE, Uges DRA, Scaf AHJ, Sleijfer DTh, et al. Pharmacokinetics of carboplatin at a dose of 750 mg/m2 divided over three consecutive days. British Journal of Cancer 61: 460–464, 1990

    Article  PubMed  CAS  Google Scholar 

  • NCI. Investigational drugs: chemical information, pp. 87–90, 170–172, 1988

  • Newell DR, Eeles RA, Gumbrell LA, Boxall FE, Horwich A, et al. Carboplatin and etoposide pharmacokinetics in patients with testicular teratoma. Cancer Chemotherapy and Pharmacology 23: 367–372, 1989

    Article  PubMed  CAS  Google Scholar 

  • Newell DR, Siddik ZH, Gumbrell LA, Boxall FE, Gore ME, et al. Plasma free platinum pharmacokinetics in patients treated with high dose carboplatin. European Journal of Cancer and Clinical Oncology 23: 1399–1405, 1987

    Article  CAS  Google Scholar 

  • Newell DR, Siddik ZH, Harrap KR. HPLC analysis of cisplatin analogues in biological fluids. In Reid & Wilson (Eds) Drug determination in therapeutic and forensic contexts, pp. 145–153, Plenum Press, New York, 1985

    Google Scholar 

  • Nygren O, Vaughan GT, Florence TM, Morrison GMP, Warner IM, et al. Determination of platinum in blood by adsorptive voltammetry. Analytical Chemistry 62: 1637–1640, 1990

    Article  PubMed  CAS  Google Scholar 

  • Oguri S, Sakakibara T, Mase H, Shimizu T, Ishikawa K, et al. Clinical pharmacokinetics of carboplatin. Journal of Clinical Pharmacology 28: 208–215, 1988

    PubMed  CAS  Google Scholar 

  • Owens SE, Thatcher N, Sharma H, Adam N, Harrison R, et al. In vivo distribution studies of radioactively labelled platinum complexes: cis-dichlorodiammine platinum(II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum(IV), cis-dichloro-bis-cyclopropylamine platinum(II), and cis-diammine 1,1-cyclobutanedicarboxylate platinum(II) in patients with malignant disease, using a gamma camera. Cancer Chemotherapy and Pharmacology 14: 253–257, 1985

    Article  PubMed  CAS  Google Scholar 

  • Ozols RF. Optimal dosing with carboplatin. Seminars in Oncology 16 (Suppl. 5): 14–18, 1989

    PubMed  CAS  Google Scholar 

  • Parsons PJ, Morrison PF, LeRoy AF. Determination of platinum-containing drugs in human plasma by liquid chromatography with reductive electrochemical detection. Journal of Chromatography 385: 323–335, 1987

    Article  PubMed  CAS  Google Scholar 

  • Pfeiffer P, Bennedbaek O, Bertelsen K. Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer. Gynecologic Oncology 36: 306–311, 1990

    Article  PubMed  CAS  Google Scholar 

  • Poirier MC, Egorin MJ, Fichtinger-Schepman AMJ, Yuspa SH, Reed E. DNA adducts of cisplatin and carboplatin in tissues of cancer patients. IARC Scientific Publications 89: 313–320, 1988

    PubMed  Google Scholar 

  • Reece PA, Bishop JF, Olver IN, Stafford I, Hillcoat BL, Morstyn G. Pharmacokinetics of unchanged carboplatin (CBDCA) in patients with small cell lung carcinoma. Cancer Chemotherapy and Pharmacology 19: 326–330, 1987

    Article  PubMed  CAS  Google Scholar 

  • Reece PA, Stafford I, Russell J, Gill PG. Nonlinear renal clearance of ultrafilterable platinum in patients treated with cis-dichlorodiammineplatinum(II). Cancer Chemotherapy and Pharmacology 15: 295–299, 1985

    Article  PubMed  CAS  Google Scholar 

  • Reed E, Ostchega Y, Steinberg SM, Yuspa SH, Young RC, et al. Evaluation of platinum-DNA adduct levels relative to known prognostic variables in a cohort of ovarian cancer patients. Cancer Research 50: 2256–2260, 1990

    PubMed  CAS  Google Scholar 

  • Reed E, Ozols RF, Tarone R, Yuspa SH, Poirier MC. Platinum-DNA adducts in leukocyte DNA correlate with disease response in ovarian cancer patients receiving platinum-based chemotherapy. Proceedings of the National Academy of Science 84: 5024–5028, 1987

    Article  CAS  Google Scholar 

  • Repta AJ, Long DF. Reactions of cisplatin with human plasma and plasma fractions. In Prestayko et al. (Eds) Cisplatin: current status and new developments, pp. 285–304, Academic Press, Inc., New York, 1980

    Google Scholar 

  • Rothenberg ML, Ostchega Y, Steinberg SM, Young RC, Hummel S, et al. High-dose carboplatin with diethyldithiocarbamate chemoprotection in treatment of women with relapsed ovarian cancer. Journal of the National Cancer Institute 80: 1488–1492, 1988

    Article  PubMed  CAS  Google Scholar 

  • Sasaki Y, Tamura T, Eguchi K, Shinkai T, Fujiwara Y, et al. Pharmacokinetics of (glycolato-0,0′)-diammine platinum(II), a new platinum derivative, in comparison with cisplatin and carboplatin. Cancer Chemotherapy and Pharmacology 23: 243–246, 1989

    Article  PubMed  CAS  Google Scholar 

  • Schmalbach TK, Borch RF. Diethyldithiocarbamate modulation of murine bone marrow toxicity induced by cis-diammine(cyclobutanedicarboxylato)platinum(II). Cancer Research 49: 6629–6633, 1989

    PubMed  CAS  Google Scholar 

  • Sharma H, Thatcher N, Baer J, Zaki A, Smith A, et al. Blood clearance of radioactively labelled cis-diammine 1,1-cyclobutane dicarboxylate platinum(II) (CBDCA) in cancer patients. Cancer Chemotherapy and Pharmacology 11: 5–7, 1983

    Article  PubMed  CAS  Google Scholar 

  • Sharma H, Tinker ND, McAuliffe CA, Lind MJ, Smith DB, et al. Ip versus iv pharmacokinetics in patients using radiolabelled paraplatin. In Nicolini (Ed.) Platinum and other metal coordination compounds in cancer chemotherapy, pp. 508–516, Martinus Nijhoff Publishing, Boston, 1988

    Chapter  Google Scholar 

  • Shea TC, Flaherty M, Elias A, Eder JP, Antman K, et al. A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support. Journal of Clinical Oncology 7: 651–661, 1989

    PubMed  CAS  Google Scholar 

  • Siddik ZH, Boxall FE, Harrap KR. Tissue solubilisation in hyamine hydroxide for the flameless atomic absorption spectrophotometric determination of platinum. In McBrien & Slater (Eds) Biomedical mechanisms of platinum antitumour drugs, pp. 355–360, IRL Press Limited, Oxford, 1986a

    Google Scholar 

  • Siddik ZH, Dible SE, Boxall RE, Harrap KR. Renal pharmacokinetics and toxicity of cisplatin and carboplatin in animals. In McBrien & Slater (Eds) Biomedical mechanisms of platinum antitumor drugs, pp. 171–198, IRL Press Limited, Oxford, 1986b

    Google Scholar 

  • Siddik ZH, Jones M, Boxall FE, Harrap KR. Comparative distribution and excretion of carboplatin and cisplatin in mice. Cancer Chemotherapy and Pharmacology 21: 19–24, 1988

    Article  PubMed  CAS  Google Scholar 

  • Siddik ZH, Newell DR, Boxall FE, Harrap KR. The comparative pharmacokinetics of carboplatin and cisplatin in mice and rats. Biomedical Pharmacology 36: 1925–1932, 1987

    CAS  Google Scholar 

  • Siddik ZH, Newell DR, Boxall FE, Jones M, McGhee KG, et al. Biliary excretion, renal handling and red cell uptake of cisplatin and CBDCA in animals. In Hacker et al. (Eds) Platinum coordination complexes in cancer chemotherapy, pp. 90–102, Martinus Nijhoff Publishing, Boston, 1984

    Chapter  Google Scholar 

  • Smeyers-Verbeke J, Detaevernier MR, Denis L, Massart DL. The determination of platinum in biological fluid by means of graphite furnace atomic absorption spectrometry. Clinica Chimica Acta 113: 329–333, 1981

    Article  CAS  Google Scholar 

  • Taguchi J, Saijo N, Miura K, Shinkai T, Eguchi K, et al. Prediction of hematologic toxicity of carboplatin by creatinine clearance rate. Japanese Journal of Cancer Research 78: 977–982, 1987

    PubMed  CAS  Google Scholar 

  • Ten Bokkel Huinink WW, Dubbelman R, Aartsen E, Franklin H, McVie JG. Experimental and clinical results with intraperitoneal cisplatin. Seminars on Oncology 12 (Suppl. 4): 43–46, 1985

    Google Scholar 

  • Ten Bokkel Huinink WW, Rodenhuis S, Simonetti G, Dubbelman R, Franklin H, et al. Studies with carboplatin in ovarian cancer. In Bunn et al. (Eds) Carboplatin (JM-8) current perspectives and future directions, pp. 165–175, WB Saunders Co., Philadelphia, 1990

    Google Scholar 

  • Ten Bokkel Huinink WW, Van der Vijgh WJF, Dubbelman R, Heintz APM, Franklin H. Platinum coordination derivatives by the intraperitoneal route: pharmacokinetics and clinical results. In Nicolini (Ed.) Platinum and other metal coordination compounds in cancer chemotherapy, pp. 367–374, Martinus Nijhoff Publishing, Boston, 1988

    Chapter  Google Scholar 

  • Ten Bokkel Huinink WW, Wanders J, Dubbelman R, Van Wijk A, Van Vliet A, et al. High dose carboplatin in refractory ovarian cancer: a phase II trial assessing the protective role against myelosuppression by diethyldithiocarbamate (DDTC). Proceedings of the 4th European Conference on Clinical Oncology and Cancer Nursing, Madrid, November 1–4, p. 214, 1987

  • Terheggen PMAB, Begg AC, Emondt JY, Dubbelman R, Floot BGJ, et al. Formation of interaction products of carboplatin with DNA in vitro and in cancer patients. British Journal of Cancer 63: 195–200, 1991

    Article  PubMed  CAS  Google Scholar 

  • Tinker ND, Sharma HL, McAuliffe CA. Qualitative investigation, both in vivo and in vitro, of the metabolites formed by cisplatin and paraplatin involving high performance liquid chromatography analysis. In Nicolini (Ed.) Platinum and other metal coordination compounds in cancer chemotherapy, pp. 144–159, Martinus Nijhoff Publishing, Boston, 1987

    Google Scholar 

  • Tjioe PS, Kroon JJ, Lelieveld P, Van der Vijgh WJF. Trace-element levels in tissues of rats and dogs treated with cis-diammine(1, 1-cyclobutahedicarboxylato)platinum-(II)(carboplatin). Journal of Radioanalytical and Nuclear Chemistry 104: 103–114, 1986

    Article  CAS  Google Scholar 

  • Tosetti F, Rocco M, Fulco RA, Chiara S, Bruzzone M, et al. Serial determination of platinum, protein content and free sulfhydryl levels in plasma of patients treated with cisplatin or carboplatin. Anticancer Research 8: 381–386, 1988

    PubMed  CAS  Google Scholar 

  • Treskes M, Holwerda U, Klein I, Pinedo HM, Van der Vijgh WJF. Chemical inactivation of cisplatin and carboplatin by the modulating agent WR2721 and its main metabolites WR1065 and WR33287. Proceedings of the 6th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, San Diego, January 23–26, Abstract no. P-62, 1991a

  • Treskes M, Nijtmans L, Fichtinger-Schepman AMJ, Holwerda U, Pinedo HM, et al. Formation and stability of interaction products formed by cisplatin with DNA or proteins in the absence and the presence of the modulating agent WR2721 and its main metabolites WR1065 and WR33278 in comparison to thiosulphate (TS) and diethyldithiocarbamate (DDTC). Proceedings of the 6th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, San Diego, January 23–26, Abstract no. P-61, 1991b

  • Treskes M, Nijtmans LGJ, Holwerda U, Fichtinger-Schepman AMJ, Pinedo HM, et al. The protective agent WR-2721 in combination with cisplatin (CDDP) and carboplatin (CBDCA): Mechanistic in-vitro studies. Abstract no. 2443. Proceedings of the American Association for Cancer Research, Houston, 1991c

  • Trump DL, Grem JL, Tutsch KD, Willson JKV, Simon KJ, Alberti D, et al. Platinum analogue combination therapy: cisplatin and carboplatin — a phase I trial with pharmacokinetic assessment of the effect of cisplatin administration on carboplatin excretion. Journal of Clinical Oncology 5: 1281–1289, 1987

    PubMed  CAS  Google Scholar 

  • Tyczkowska K, Page RL, Riviere JE. Determination of carboplatin in canine plasma by liquid chromatography with ultraviolet-visible detection and confirmation by atomic absorption spectroscopy. Journal of Chromatography 527: 447–453, 1990

    Article  PubMed  CAS  Google Scholar 

  • Van der Vijgh WJF, Elferink F, Vermorken JB, Ten Bokkel Huinink WW, Klein I, et al. Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of aqua (1,1-bis(aminomethyl)cyclohexane)sulfatoplatinum(II) (Spiroplatin) during a phase I trial. European Journal of Cancer and Clinical Oncology 24: 621–627, 1988

    Article  Google Scholar 

  • Van der Vijgh WJF, Klein I. Protein binding of five platinum compounds. Comparison of two ultrafiltration systems. Cancer Chemotherapy and Pharmacology 18: 129–132, 1986

    Article  PubMed  Google Scholar 

  • Van der Vijgh WJF, Lelieveld P, Klein I, Van Putten LM, Pinedo HM. Pharmacokinetics of five platinum compounds in dogs. In Spitzy & Karrer (Eds) New drugs in cancer chemotherapy, Proceedings of the 13th International Congress of Chemotherapy, Vol. 286, pp. 57–59, Vienna, 1983

    Google Scholar 

  • Van Echo DA, Egorin MJ, Aisner J. The pharmacology of carboplatin. Seminars in Oncology 16 (Suppl. 5): 1–6, 1989

    PubMed  Google Scholar 

  • Van Echo DA, Egorin MJ, Whitacre MY, Olman EA, Aisner J. Phase I clinical and pharmacologic trial of carboplatin daily for 5 days. Cancer Treatment Reports 68: 1103–1114, 1984

    PubMed  Google Scholar 

  • Van Hennik MB, Van der Vijgh WJF, Klein I, Elferink F, Vermorken JB, et al. Comparative pharmacokinetics of cisplatin and three analogues in mice and humans. Cancer Research 47: 6297–6301, 1987

    PubMed  Google Scholar 

  • Van Hennik MB, Van der Vijgh WJF, Klein I, Vermorken JB, Pinedo HM. Human pharmacokinetics of carboplatin after oral administration. Cancer Chemotherapy and Pharmacology 23: 126–127, 1989

    Article  PubMed  Google Scholar 

  • Vermorken JB, Van der Vijgh WJF, Klein I, Gall HE, Van Groeningen CJ, et al. Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin. Clinical Pharmacology and Therapeutics 39: 136–144, 1986

    Article  PubMed  CAS  Google Scholar 

  • Vermorken JB, Van der Vijgh WJF, Klein I, Hart AAM, Gall HE, et al. Pharmacokinetics of free and total platinum species after short-term infusion of cisplatin. Cancer Treatment Reports 68: 505–513, 1984

    PubMed  CAS  Google Scholar 

  • Vermorken JB, Winograd B, Van der Vijgh WJF. Clinical pharmacology of cisplatin and some new platinum analogs. In Ishigami (Ed.) Recent advances in chemotherapy, Proceedings of the 14th Congress of Chemotherapy, pp. 96–99, University of Tokyo Press, Tokyo, 1985

    Google Scholar 

  • Vlasveld LT, Beynen JH, Boogerd W, Ten Bokkel Huinink WW, Rodenhuis S. Complete remission of brain metastases of ovarian cancer following high-dose carboplatin: a case report and pharmacokinetic study. Cancer Chemotherapy and Pharmacology 25: 382–383, 1990

    Article  PubMed  CAS  Google Scholar 

  • Wagstaff AJ, Ward A, Benfield P, Heel RC. Carboplatin: a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of cancer. Drugs 37: 162–190, 1989

    Article  PubMed  CAS  Google Scholar 

  • Woolley PV, Priego VM, Luc PVT, Rahman A, Schein PS. Clinical pharmacokinetics of diammine[1,1-cyclobutanecarboxylato (2)]-0,0′Platinum (CBDCA). In Hacker et al. (Eds) Platinum coordination complexes in cancer chemotherapy, pp. 82–89, Martinus Nijhoff Publications, Boston, 1984

    Chapter  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Free University Hospital, Room BR234, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands

    Wim J. F. van der Vijgh

Authors
  1. Wim J. F. van der Vijgh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

van der Vijgh, W.J.F. Clinical Pharmacokinetics of Carboplatin. Clin. Pharmacokinet. 21, 242–261 (1991). https://doi.org/10.2165/00003088-199121040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199121040-00002

Keywords

Search

Navigation