Phase I safety and pharmacokinetic studies of brequinar sodium after single ascending oral doses in stable renal, hepatic, and cardiac allograft recipients

Journal of Clinical Pharmacology

Volumn 37, Issue 12, 1997, Pages 1121-1128

  Joshi, Amita S ^a,c   King, Shang Ying P ^a   Zajac, Barbara A ^a   Makowka, Leonard ^a   Sher, Linda S ^b   Kahan, Barry D ^b   Menkis, Alan H ^b   Stiller, Calvin R ^b   Schaefle, Brigitte ^c   Kornhauser, David M ^c  

^a Department of Drug Metabolism and Pharmacokinetics ^*  (United States)

^b Du Pont Merck Pharmaceutical   (United States)

^c DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BREQUINAR; CYCLOSPORIN A; PREDNISONE;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CLINICAL PROTOCOL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG SAFETY; FEMALE; GRAFT REJECTION; HEADACHE; HEART TRANSPLANTATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY ALLOGRAFT; LIVER TRANSPLANTATION; MALE; MULTICENTER STUDY; NAUSEA; ORAL DRUG ADMINISTRATION; PHASE 1 CLINICAL TRIAL; RECIPIENT;

EID: 0031424049     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1002/j.1552-4604.1997.tb04296.x     Document Type: Article

References (18)

1. Cramer DV, Chapman FA, Jaffee BD, Jones EA, Knoop M, Hreha-Eiras G, Makowka L: The effect of a new immunosuppressive drug, brequinar sodium, on cardiac, hepatic, and renal allograft rejection in the rat. Transplantation 1992;53:303-308.
2. Cramer DV, Knoop M, Chapman FA, Wu G-D, Jaffee BD, Makowka L: Prevention of liver allograft rejection in rats by a short course of therapy with brequinar sodium. Transplantation 1992;54:752-753.
3. Cramer DV, Chapman FA, Jaffee BD, Zajac I, Hreha-Eiras G, Yasunaga C, Wu G-D, Makowka L: The prolongation of concordant hamster-to-rat cardiac xenografts by brequinar sodium. Transplantation 1992:54:403-408.
4. Makowka L, Chapman F, Cramer DV: Historical development of brequinar sodium as a new immunosuppressive drug for transplantation. Transpl Proc 1993:25:2-7.
5. Stepkowski SM, Yu T, Chou T-C, Kahan BD: Synergistic interaction of cyclosporine, rapamycin, and brequinar on cardiac allograft survival in mice. Transpl Proc 1994:26:3025-3027.
6. G. Chen S-F, Ruben RL, Dexter DL: Mechanism of action of the novel anticancer agent DuP 785 [G-fluoro-2-(2'-fluoro-l,l'-biphenyl-4-yl)-3-methyl-4-quinolinecarboxylic acid sodium salt]: inhibition of de novo pyrimidine nucleotide biosynthesis. Cancer Res 1989:46:5014-5019.
7. Kahan BD, Tejpal N, Gibbons-Slubbers S, Tu Y, Wang M, Stepkowski S, Chou T-C: The synergistic interactions in vitro and in vivo of brequinar sodium with cyclosporine or rapamycin alone and in triple combination. Transplantation 1993:55:894-900.
8. Arteaga CL, Brown TD, Kühn JG, Shen H-SL, O'Rourke TJ, Beougher K, et al: Phase I clinical and pharmacokinetic trial of brequinar sodium (DuP 785; NSC368390). Cancer Res 1989:49:4648-4653.
9. Bork E, Vest S, Hansen HH: A phase I clinical and pharmacokinetic study of brequinar sodium, DuP 785 (NSC 368390), using a weekly and a biweekly schedule. Eur J Cancer Clin Oncol 1989;25:1403-1411.
10. Noe DA, Rowinsky EK, Shen H-SL, Clarke BV, Grochow LD, McGuire WB, et al: Phase I and pharmacokinetic study of brequinar sodium (NSC 368390). Cancer Res 1990;50:4595-4599.
11. Schwartsmann G, VanDerVijgh W, VanHennic M, Klein I, Vermorken J, Dodion P, et al: Pharmacokinetics of brequinar sodium (NSC 368390) in patients with solid tumors during a phase I study. Eur J Cancer Clin Oncol 1989:25:1675-1681.
12. Schwartsmann G, Dodion P, Vermorken J, Huinink W, Joggi J, Winograd B, et al: Phase I study of brequinar sodium (NSC 368390) in patients with solid malignancies. Cancer Chemother Pharmacol 1990:25:345-351.
13. Currie VE, O'Hehir M, Blatzer L, Slavik W, Yaldaei S, Bertino J: Phase I trial of DuP 785 given on a single weekly intravenous dosing schedule. Proc Am Soc Clin Oncol 1988; 7:76.
14. King S-YP, Agra AM, Shen H-SL, Chi CL, Adams DB, Currie VE, et al: Protein binding of brequinar in the plasma of healthy donors and cancer patients and analysis of tho relationship between protein binding and pharmacokinetics in cancer patients. Cancer Chemother Pharmacol 1994;35:101-108.
15. Gibaldi M, Perrier D: Pharmacokinetics. Second edition. New York: Marcel Dekker, 1982.
16. Lam FC, Hung CT, Perrier DG: Estimation of variance for harmonic mean half-lives. J Pharm Sci 1985:74:229-231.
17. Kronbach T, Fischer V, Meyer UA: Cyclosporin metabolism in human liver: identification of a cytochrome P-450HI gene family as the major cyclosporin metabolizing enzyme explains interactions of cyclosporin with other drugs. Clin Pharmacol Ther 1988:43:630-635.
18. Yee GC, McGuire TR: Pharmacokinetic drug interactions with cyclosporin. Clin Pharmacokinet 1990; 19:400-415.