METABOLIC-CLEARANCE OF RECOMBINANT HUMAN GROWTH-HORMONE IN HEALTH AND CHRONIC-RENAL-FAILURE

被引:108
作者
HAFFNER, D
SCHAEFER, F
GIRARD, J
RITZ, E
MEHLS, O
机构
[1] UNIV HEIDELBERG, DEPT PEDIAT, W-6900 HEIDELBERG, GERMANY
[2] UNIV HEIDELBERG, DEPT INTERNAL MED, W-6900 HEIDELBERG, GERMANY
[3] UNIV BASEL, CHILDRENS HOSP, BASEL, SWITZERLAND
关键词
GROWTH HORMONE; PHARMACOKINETICS; RENAL FAILURE; METABOLIC CLEARANCE; HALF-LIFE;
D O I
10.1172/JCI117069
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Despite the increasing therapeutic use of recombinant human growth hormone(rhGH), its metabolic clearance has not been investigated in detail. To evaluate the kinetics of rhGH as a possible function of GH plasma concentration and glomerular filtration rate (GFR), we investigated the steady state metabolic clearance rate (MCR), disappearance half-life, and apparent volume of distribution of rhGH at low and high physiological as well as supraphysiological plasma GH levels during pharmacological suppression of endogenous GH secretion in human subjects with normal and reduced renal function. GH in plasma and urine was determined by an immunoradiometric assay, and GFR by inulin clearance. In all subjects MCR decreased and plasma half-life increased with increasing plasma GH concentrations (P < 0.001). MCR of rhGH was approximately half in patients with chronic renal failure at each GH level and plasma half-life was increased by 25-50%. Allowing for the linear dependence of MCR on GFR and assuming single-compartment distribution, the estimated renal fraction of total MCR was 25-53 and 4-15% in controls and patients, respectively. Saturation of extrarenal disposal of GH was suggested by an inverse hyperbolic relationship between extrarenal MCR and plasma GH concentrations in all subjects. Fractional GH excretion was up to 1,000-fold higher in patients than in controls. We conclude that MCR of hGH is a function of plasma GH concentrations and GFR. Extrarenal elimination is saturable in the upper physiological range of GH concentrations, whereas renal MCR is independent of plasma GH levels. The kidney handles GH like a microprotein involving glomerular filtration, tubular reabsorption, and urinary excretion.
引用
收藏
页码:1163 / 1171
页数:9
相关论文
共 56 条
[1]   A SPECIFIC GROWTH HORMONE-BINDING PROTEIN IN HUMAN-PLASMA - INITIAL CHARACTERIZATION [J].
BAUMANN, G ;
STOLAR, MW ;
AMBURN, K ;
BARSANO, CP ;
DEVRIES, BC .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1986, 62 (01) :134-141
[2]   THE EFFECT OF CIRCULATING GROWTH HORMONE-BINDING PROTEIN ON METABOLIC-CLEARANCE, DISTRIBUTION, AND DEGRADATION OF HUMAN GROWTH-HORMONE [J].
BAUMANN, G ;
AMBURN, KD ;
BUCHANAN, TA .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1987, 64 (04) :657-660
[3]   THE CIRCULATING GROWTH-HORMONE (GH)-BINDING PROTEIN COMPLEX - A MAJOR CONSTITUENT OF PLASMA GH IN MAN [J].
BAUMANN, G ;
AMBURN, K ;
SHAW, MA .
ENDOCRINOLOGY, 1988, 122 (03) :976-984
[4]   URINARY GROWTH-HORMONE IN MAN - EVIDENCE FOR MULTIPLE MOLECULAR-FORMS [J].
BAUMANN, G ;
ABRAMSON, EC .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1983, 56 (02) :305-311
[5]   ISOLATION AND PARTIAL CHARACTERIZATION OF 6 SOMATOMEDIN-LIKE PEPTIDES FROM HUMAN-PLASMA COHN FRACTION-IV [J].
BLUM, WF ;
RANKE, MB ;
BIERICH, JR .
ACTA ENDOCRINOLOGICA, 1986, 111 (02) :271-284
[6]   A SPECIFIC RADIOIMMUNOASSAY FOR INSULIN-LIKE GROWTH FACTOR-II - THE INTERFERENCE OF IGF BINDING-PROTEINS CAN BE BLOCKED BY EXCESS IGF-I [J].
BLUM, WF ;
RANKE, MB ;
BIERICH, JR .
ACTA ENDOCRINOLOGICA, 1988, 118 (03) :374-380
[7]   GROWTH-HORMONE RESISTANCE AND INHIBITION OF SOMATOMEDIN ACTIVITY BY EXCESS OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN IN UREMIA [J].
BLUM, WF ;
RANKE, MB ;
KIETZMANN, K ;
TONSHOFF, B ;
MEHLS, O .
PEDIATRIC NEPHROLOGY, 1991, 5 (04) :539-544
[8]   A SPECIFIC RADIOIMMUNOASSAY FOR THE GROWTH-HORMONE (GH)-DEPENDENT SOMATOMEDIN-BINDING PROTEIN - ITS USE FOR DIAGNOSIS OF GH DEFICIENCY [J].
BLUM, WF ;
RANKE, MB ;
KIETZMANN, K ;
GAUGGEL, E ;
ZEISEL, HJ ;
BIERICH, JR .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1990, 70 (05) :1292-1298
[10]  
BULLIEPICARD F, 1988, J ENDOCRINOL, V121, P19