Pharmacokinetics and pharmacodynamics of a recombinant human granulocyte colony-stimulating factor

被引:78
作者
Kuwabara, T
Kobayashi, S
Sugiyama, Y
机构
[1] UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU,TOKYO 113,JAPAN
[2] KYOWA HAKKO KOGYO CO LTD,PHARMACEUT RES LABS,NAGAIZUMI,SHIZUOKA 411,JAPAN
关键词
D O I
10.3109/03602539608994020
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor, is a clinically effective drug used to promote neutrophil recovery in patients with chemo- or radiotherapy-induced neutropenia. We have reviewed the pharmacokinetic and pharmacodynamic properties of three kinds of G-CSFs: E. coli derived G-CSF, CHO-derived G-CSF, and mutein G-CSF. The clearances of G-CSFs are saturable and autoinducible in experimental animals and humans. That is, the systemic clearances of G-CSFs decrease as the dose injected increases and approaches a constant value. Both saturable and nonsaturable processes are involved in G-CSF elimination. Also, the systemic clearances of G-CSFs are increased by repeated administration of G-CSF. Although the relative bioavailability of G-CSFs after subcutaneous administration is approximately 60%, the increase in peripheral white blood cells or neutrophils is greater than that after intravenous administration at the same dose. The effects of G-CSFs seem to be time dependent rather than AUC dependent, considering that mean residence time of G-CSFs in the plasma is longer after subcutaneous administration than that after intravenous administration. There is a slight difference in the pharmacokinetics of E-coli- and CHO-G-CSF although they seem to be pharmacologically equivalent. The correlation between G-CSF clearance and peripheral neutrophil counts in the patients suggests that G-CSF receptors contribute to G-CSF clearance. Quantitative pharmacokinetic analysis using mutein G-CSF shows that the G-CSF receptor plays a major role in saturable G-CSF clearance, and that this saturable process accounts for approximately 80% of the total clearance at low doses. That is, the degradation following the receptor-mediated endocytosis in bone marrow might be a major clearance system of G-CSF at a physiological blood level. The G-CSF receptor in bone marrow might work not only as a signal transducer for differentiation and proliferation of granulopoietic precursor cells but as a regulator of G-CSF levels in blood. In addition, at high doses, glomerular filtration in the kidneys is the major process for nonsaturable G-CSF clearance. At present, polyethylene glycol derivatives of G-CSF are being developed to reduce the frequency of G-CSF administration.
引用
收藏
页码:625 / 658
页数:34
相关论文
共 66 条
[1]  
Asano M, 1991, JPN PHARMACOL THER, V19, P373
[2]  
BAUER RJ, 1994, J PHARMACOL EXP THER, V268, P152
[3]   PHARMACOKINETIC PROPERTIES OF POLYETHYLENE-GLYCOL DERIVATIZED SUPEROXIDE-DISMUTASE [J].
BOCCU, E ;
VELO, GP ;
VERONESE, FM .
PHARMACOLOGICAL RESEARCH COMMUNICATIONS, 1982, 14 (02) :113-120
[4]  
BROUCHUD MH, 1987, BRIT J CANCER, V56, P809
[5]   THE HUMAN HEMATOPOIETIC COLONY-STIMULATING FACTORS [J].
CLARK, SC ;
KAMEN, R .
SCIENCE, 1987, 236 (4806) :1229-1237
[6]  
COHEN AM, 1987, P NATL ACAD SCI USA, V84, P2284
[7]  
DEMETRI GD, 1991, BLOOD, V78, P2791
[8]   GRANULOCYTE COLONY-STIMULATING FACTOR - PRECLINICAL AND CLINICAL-STUDIES [J].
GABRILOVE, JL ;
JAKUBOWSKI, A .
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 1989, 3 (03) :427-440
[9]   EFFECT OF AMINOPHYLLINE ON CISPLATIN NEPHROTOXICITY IN THE RAT [J].
HEIDEMANN, HT ;
MULLER, S ;
MERTINS, L ;
STEPAN, G ;
HOFFMANN, K ;
OHNHAUS, EE .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 97 (02) :313-318
[10]   PHARMACODYNAMICS OF DAILY SUBCUTANEOUS RECOMBINANT HUMAN INTERLEUKIN-3 IN NORMAL VOLUNTEERS [J].
HUHN, RD ;
YURKOW, EJ ;
KUHN, JG ;
CLARKE, L ;
GUNN, H ;
RESTA, D ;
SHAH, R ;
MYERS, LA ;
SEIBOLD, JR .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1995, 57 (01) :32-41