ANALYSIS OF RADIOLABELED CHO CELL-DERIVED RHUGM-CSF PHARMACOKINETICS AND BIODISTRIBUTION IN RHESUS-MONKEYS FOLLOWING INTRAVENOUS AND SUBCUTANEOUS INJECTION

被引:3
作者
BURCHIEL, SW
OETTE, D
DAY, PW
STOLL, RE
机构
[1] UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131
[2] SANDOZ PHARMACEUT CORP,E HANOVER,NJ 07936
来源
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY | 1994年 / 16卷 / 02期
关键词
RHUGM-CSF; BIODISTRIBUTION; IMAGING; PHARMACOKINETICS; RHESUS MONKEYS;
D O I
10.1016/0192-0561(94)90063-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The purpose of these studies was to examine the biodistribution and pharmacokinetics of radiolabeled human CHO cell-derived rHuGM-CSF in normal Rhesus monkeys (Macaca mulatta) following intravenous (i.v.) and subcutaneous (s.c.) injection. A dual radioisotope tracer technique was utilized to monitor the behavior of rHuGM-ChF in vivo. Recombinant HuGM-CSF was radiolabeled with I-123 (a 13.2 h half-life, 140 KeV pure gamma emitting radionuclide detected using gamma scintigraphic imaging) using a mild chloramine T reaction. A separate preparation of rHuGM-CSF radiolabeled with S-35 methionine by bioincorporation in tissue culture was mixed with the I-123-labeled protein, permitting comparison of data obtained from the two radiolabels. Two dose levels of rHuGM-ChF were used for i.v. bolus (15 and 300 mu g/kg) and s.c. (10 and 100 mu g/kg) studies. The results of these studies demonstrated that the co-administered I-123 rHuGM-ChF and S-35 rHuGM-CSF followed similar blood elimination kinetics after i.v. or s.c. injection. Following i.v. bolus injection, rHuGM-CSF was found to rapidly distribute to all central body cavity high blood flow organs, followed by rapid uptake in the kidneys and elimination in the urine. There were no differences in the pharmacokinetic values obtained for I-123- and S-35-labeled rHuGM-CSF nor for the two dose levels examined. Following, s.c. injection, I-123- and S-35-labeled rHuGM-CSF were found to reach maximal plasma levels after approximately 16 h. The primary route of elimination was the urine. Monkeys previously exposed to rHuGM-CSF were found to have circulating antibodies to rHuGM-CSF. Studies in these animals revealed a significantly altered distribution and clearance of radiolabeled rHuGM-CSF, with the majority of the injected activity being cleared by the liver.
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页码:75 / &
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