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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Apr;84(4):468–473. doi: 10.1111/j.1349-7006.1993.tb00160.x

Pharmacokinetic Evaluation of (Glycolato‐O, O′) diammine Platinum(II) in Lung Lymph in Sheep

Tomonobu Koizumi 1,✉, Keishi Kubo 1, Shirou Shinozaki 1, Shigeru Koyama 1, Toshiya Amari 3, Toshihide Hayano 1, Keisaku Fujimoto 1, Toshio Kobayashi 1, Morie Sekiguchi 1, Ryosuke Sakai 2, Taeyuki Ohshima 3, Ken‐ichi Miyamoto 3
PMCID: PMC5919307  PMID: 8514614

Abstract

The pharmacokinetics of (glycolato‐O, O′)diammine platinum(II) (254‐S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis‐diammine‐dichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and a lung lymph fistula, respectively, in conscious sheep following intravenous infusion of 100 mg/body of 254‐S and CDDP for 30 min. The concentrations of these platinum complexes were measured by using atomic absorption spectrometry. We analyzed the data using an anatomically based model including part of the lymphatic circulation. The ultrafilterable platinum of 254‐S showed much larger area under the curve (AUC) and transfer rate constants than that of CDDP, even though the mean residence times were the same. The total platinum showed the opposite pharmacokinetic behavior. In anesthetized sheep, when lung tissue samples were obtained by biopsy at the same times as those of blood and lung lymph sampling after infusion of these drugs, 254‐S distributed in lung tissue appeared to move more easily into lung lymph than CDDP, which tended to be retained in lung tissue. These differences in pharmacokinetic behavior between 254‐S and CDDP seemed to be caused by differences in their strength of protein binding, the association constants of 254‐S for plasma and lymph protein were much less than those of CDDP. From these results, 254‐S may have favorable therapeutic effects on intrathoracic malignacies such as lung cancer and lymph metastasis

Keywords: Pharmacokinetics, Cisplatin, 254‐S, Lung lymph, Sheep

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REFERENCES

  • 1. ) Gralla , R. J. , Cvitkovi , E. and Golbey , R. B.cis‐Di‐chlorodiammineplatinum(II) in non‐small cell carcinoma of the lung . Cancer Treat. Rep. , 63 , 1585 – 1588 ( 1979. ). [PubMed] [Google Scholar]
  • 2. ) Gralla , R. J. , Casper , E. S. , Kelsen , D. P. , Braun , D. W. , Dukeman , M. E. , Martini , N. , Young , C. W. and Golbey , R. B.Cisplatin and vindesine combination chemotherapy for advanced carcinoma of the lung: a randomized trial investigating two dosage schedules . Ann. Intern. Med. , 95 , 414 – 420 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Shinkai , T. , Saijo , N. , Tominaga , K. , Eguchi , K. , Shimizu , E. , Sasaki , Y. , Fujita , J. and Futami , H.Comparison of vindesine plus cisplatin or vindesine plus mitomycin in the treatment of advanced non‐small cell lung cancer . Cancer Treat. Rep. , 69 , 945 – 951 ( 1985. ). [PubMed] [Google Scholar]
  • 4. ) Shiratori , O. , Kanai , H. , Uchida , N. , Takeda , Y. , Totani , T. and Sato , K.Antitumor activity of 254‐S, a platinum complex, in rodents . In “ Recent Advances in Chemotherapy ,” ed. Ishigami J. , pp. 635 – 636 ( 1985. ). University of Tokyo Press; , Tokyo . [Google Scholar]
  • 5. ) Totani , T. , Aono , K. , Adachi , Y. , Komura , M. , Shiratori , O. and Sato , K.Bidentate hydroxycarboxylic and platinum(II) complexes with antitumor activity . In “ Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy ,” ed. Nicolini M. , pp. 744 – 748 ( 1988. ). Martinus Nijhoff Publishing; , Boston . [Google Scholar]
  • 6. ) Ariyoshi , Y. , Fujii , M. , Kurita , Y. , Ohshima , S. , Tamura , M. , Inoue , S. , Nishiwaki , Y. , Kimura , I. and Niitani , H.Phase II clinical study of (glycolato‐O, O′)dtammine platinum(II) (254‐S), a new platinum complex, for primary lung cancer . Proc. Am. Soc. Clin. Oncol. , 8 , 927 ( 1989. ). [Google Scholar]
  • 7. ) Fukuda , M. , Shinkai , T. , Eguchi , K. , Sasaki , Y. , Tamura , T. , Ohe , Y. , Kojima , A. , Oshita , F. , Hara , K. and Saijo , N.Phase II study of (glycolate‐O, O′)diammineplatinum(II), a novel platinum complex, in the treatment of non‐small‐cell lung cancer . Cancer Chemother. Pharmacol. , 26 , 393 – 396 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) DeConti , R. C. , Toftness , B. R. , Lange , R. C. and Creasey , W. A.Clinical and pharmacological studies with cis‐diamminedichloroplatinurn(II) . Cancer Res. , 33 , 1310 – 1315 ( 1973. ). [PubMed] [Google Scholar]
  • 9. ) Owens , S. E. , Thatcher , N. , Sharma , H. , Adam , N. , Harrison , R. , Smith , A. , Zaki , A. , Baer , J. C. , McAuliffe , C. A. , Crowther , D. and Fox , B. W.In vivo distribution studies of radioactively labelled platinum complexes; cis‐dichlorodiammine platinum (II), cis‐trans‐dichlorodi‐hydroxy‐bis(isopropylamine) platinum(IV), cis‐dichlorobis‐cyclopropylamine platinum(II), and cis‐diammine l, l‐cyclobutanedicarboxylate platinum(II) in patients with malignant disease, using a gamma camera . Cancer Chemother. Pharmacol. , 14 , 253 – 257 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Sasaki , Y. , Tamura , T. , Eguchi , K. , Shinkai , T. , Fujiwara , Y. , Fukuda , M. , Ohe , Y. , Bungo , M. , Horiuchi , N. , Niimi , S. , Minato , K. , Nakagawa , K. and Saijo , N.Pharma‐cokinetics of (glycolato‐O, O′)diammine platinum(II), a new platinum derivative, in comparison with cisplatin and carboplatin . Cance Chemother. Pharmacol. , 23 , 243 – 246 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Sasaki , Y. , Amano , T. , Morita , M. , Shinkai , T. , Eguchi , K. , Tamura , T. , Ohe , Y. , Kojima , A. and 'Saijo , N.Phase I study and pharmacological analysis of cis‐diammine‐(glycolato)platinum (254‐S; NSC375101D) administered by 5‐day continuous intravenous infusion . Cancer Res. , 51 , 1472 – 1477 ( 1991. ). [PubMed] [Google Scholar]
  • 12. ) Litterst , C. L. , Gram , T. E. , Dedrick , R. L. , Leroy , A. F. and Guarino , A. M.Distribution and disposition of platinum following intravenous administration of cis‐diamminedichloroplatinum(II) (NSC 119875) to dogs . Cancer Res. , 36 , 2340 – 2344 ( 1976. ). [PubMed] [Google Scholar]
  • 13. ) Siddik , Z. H. , Jones , M. , Boxall , F. E. and Harrap , K. R.Comparative distribution and excretion of carboplatin and cisplatin in mice . Cancer Chemother. Pharmacol. , 21 , 19 – 24 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Uozumi , J. and Litterst , C. L.The effects of platinum levels in plasma, urine, and kidney on blood urea nitrogen levels after cisplatin injection in rats . J. Pharmacobio-Dyn. , 11 , 277 – 283 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Staub , N. C. , Bland , R. D. , Brigham , K. L. , Demling , R. , Erdman , A. J. and Woolverton , W. C.Preparation of chronic lung lymph fistulas in sheep . J. Surg. Res. , 19 , 315 – 320 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Meyrick , B. and Brigham , K. L.Acute effects of Escherichia coli endotoxin on the pulmonary micro‐circulation of anesthetized sheep: structure‐function relationships . Lab. Invest. , 48 , 458 – 470 ( 1983. ). [PubMed] [Google Scholar]
  • 17. ) Leroy , A. F. , Mehling , M. L. and Sponseller , H. L.Analysis of platinum in biological materials by flameless atomic absorption spectrophotometry . Biochem. Med. , 18 , 184 – 191 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Takahashi , K. , Seki , T. , Nishikawa , K. , Minamide , S. , Iwabuchi , M. , Ono , M. , Nagamine , S. and Horinishi , H.Antitumor activity and toxicity of serum protein‐bound platinum formed from cisplatin . Jpn. J. Cancer Res. , 76 , 68 – 74 ( 1985. ). [PubMed] [Google Scholar]
  • 19. ) Blanc , M. , Steimer , J. L. , Boyer , C. , Plusquellec , Y. and Cotonat , J.Isoniazid plasma and lymph kinetics after intravenous injection in dogs . Arzneim.-Forsch./Drug Res. , 34 , 1283 – 1288 ( 1984. ). [PubMed] [Google Scholar]
  • 20. ) Yamaoka , K. , Tanigawara , Y. , Nakagawa , T. and Uno , T.A pharmacokinetic analysis program (MULTI) for microcomputer . J. Pharmacobio-Dyn. , 4 , 879 – 885 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Vrein , C. E. , Snashall , P. D. , Demling , R. H. and Staub , N. C.Lung lymph and free interstitial fluid protein composition in sheep with edema . Am. J. Physiol. , 230 , 1650 – 1653 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Brigham , K. L. , Boweres , R. E. and Haynes , J.Increased sheep lung vascular permeability caused by Escherichia coliendotoxin . Circ. Res. , 45 , 292 – 297 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Kubo , K. and Kobayashi , T.Effects of OKY‐046, a selective thromboxane synthetase inhibitor, on endotoxin‐induced lung injury in unanesthetized sheep . Am. Rev. Res. Dis. , 132 , 494 – 499 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Toyofuku , T. , Koyama , S. , Kobayashi , T. , Kusama , S. and Ueda , G.Effects of polycations on pulmonary vascular permeability in conscious sheep . J. Clin. Invest. , 83 , 2063 – 2069 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Gormely , P. E. , Bull , J. M. , Leroy , A. F. and Cysyk , R.Kinetics of cis‐dichlorodiammine platinum . Clin, Pharmacol. Ther. , 25 , 351 – 357 ( 1979. ). [DOI] [PubMed] [Google Scholar]

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