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1.
Drug Metab Dispos ; 23(9): 904-9, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8565779

ABSTRACT

Recombinant human interleukin-2 (rHuIL-2) has been metabolically labeled with 14C amino acids in Escherichia coli and affinity purified on a rHuIL-2 receptor affinity column. The radiolabeled molecule had a specific radioactivity of 238 dpm/unit and the identical amino acid sequence and biological activity as unlabeled rHuIL-2. In this study, we used this labeled [14C(U)]rHuIL-2 and commercially available [125I]rHuIL-2 (identical in sequence to the [14C(U)]rHuIL-2) to compare the mass balance, pharmacokinetics, and disposition in cynomolgus monkeys. After a single intravenous bolus dose of 4 x 10(5) units/kg, serum samples were collected for 7 days and examined for biological activity, total radioactivity, and by molecular size exclusion chromatography. Urine and feces were analyzed for total radioactivity. When analyzed for biological activity, both [14C(U)]- and [125I]rHuIL-2 exhibited the following pharmacokinetic parameters: terminal elimination half-life of 1-2 hr, AUC0-infinity ranged from 2005 to 4659 units x hr/ml, clearance was 90-200 ml/hr/kg, and volume of distribution ranged from 103 to 163 ml/kg. Comparison of the pharmacokinetic profiles of the two radiolabels were very different from bioactivity, in that the elimination half-lives for radioactivity were approximately 8 days and 10 hr for [14C(U)]- and [125I]rHuIL-2, respectively. We conclude that the [14C(U)]rHuIL-2 was metabolized to constituent amino acids and recycled into newly synthesized proteins from our size exclusion chromatography studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Interleukin-2/pharmacokinetics , Amino Acids/metabolism , Animals , Carbon Radioisotopes , Cells, Cultured , Chromatography, Gel , Feces/chemistry , Half-Life , Humans , Iodine Radioisotopes , Macaca fascicularis , Male , Mice , Mice, Inbred C57BL , Recombinant Proteins/pharmacokinetics , T-Lymphocytes/metabolism , Tissue Distribution
2.
J Immunol Methods ; 168(1): 9-16, 1994 Jan 12.
Article in English | MEDLINE | ID: mdl-8288898

ABSTRACT

The detection of picogram quantities of recombinant human IL-1 alpha in human and rat serum was accomplished by a sensitive and specific two cell immunobioassay. The specificity is provided by an IL-1 alpha specific mouse IgM monoclonal antibody which is non-neutralizing thus allowing for the addition of the EL-4 NOB-1 cell line directly to the IL-1 alpha monoclonal antibody complex. The above cell line is then converted to an IL-2 producer line in response to the captured IL-1 alpha. Supernatant from the EL-4 NOB-1 cells is then added to the IL-2 dependent CTLL-2 line and cell proliferation measured by thymidine incorporation. This assay has the advantage of specificity provided by the antibody capture step, sensitivity provided by the EL-4 NOB-1 line (1-50 pg/ml) and finally ease of maintenance of the responder cell line which requires no feeder cells or mitogens. Data are reported on the sensitivity, precision, reproducibility and specificity of the assay, the stability of rhIL-1 alpha in serum and the recovery of rhIL-1 alpha from serum. We also report on the use of this procedure to assay samples from rats given ascending doses of rhIL-1 alpha.


Subject(s)
Biological Assay/methods , Immunoassay/methods , Interleukin-1/blood , Animals , Cell Division , Humans , Interleukin-1/pharmacokinetics , Male , Rats , Rats, Sprague-Dawley , Recombinant Proteins/blood , Reproducibility of Results , Sensitivity and Specificity
3.
J Biol Response Mod ; 8(4): 440-9, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2787839

ABSTRACT

Single doses of teceleukin ranging from 0.1 to 30 x 10(6) units were administered to cancer patients as intravenous infusions or subcutaneous injections. Serum samples were analyzed using a bioassay. In general, teceleukin was rapidly eliminated after intravenous administration, with half-lives ranging from 0.24 to 3.3 h. Teceleukin disappeared from serum more slowly following subcutaneous administration, with half-lives of 2.7 to 12.2 h. This finding may be a result of slow absorption from the subcutaneous injection site. Serum concentrations of teceleukin increased in an apparently dose-proportional manner following intravenous administration. When administered subcutaneously, serum concentrations increased with increasing dose but in a manner that was less than dose-proportional, possibly due to dose-dependent bioavailability for subcutaneously administered teceleukin.


Subject(s)
Interleukin-2/pharmacokinetics , Adult , Aged , Female , Humans , Infusions, Intravenous , Injections, Subcutaneous , Interleukin-2/administration & dosage , Interleukin-2/blood , Male , Middle Aged , Neoplasms/drug therapy , Recombinant Proteins/administration & dosage , Recombinant Proteins/blood , Recombinant Proteins/pharmacokinetics
4.
Anal Chem ; 61(15): 1732-6, 1989 Aug 01.
Article in English | MEDLINE | ID: mdl-2672878

ABSTRACT

A sensitive and specific assay for recombinant interleukin-2 (rIL-2) in human serum is described. The assay is based on a sequential sandwich immunobioassay that uses a microtiter plate coated with anti-rIL-2 monoclonal antibody (specific for recombinant human IL-2) to capture rIL-2 from serum, and an IL-2 dependent T-cell line that proliferates in a dose-dependent fashion. The lower limit of quantitation of the assay is 2 units/mL (1 unit = approximately 50 pg) using 0.1 mL of serum and the calibration curves ranged from 2 to 50 units/mL. Data are reported on the sensitivity, precision, reproducibility, and specificity of the assay; the stability of rIL-2 in serum; and the recovery of rIL-2 from serum. We also report on the use of the procedure to assay clinical samples from patients with AIDS undergoing treatment with rIL-2.


Subject(s)
Interleukin-2/analysis , Acquired Immunodeficiency Syndrome/blood , Antibodies, Monoclonal , Humans , Immunologic Techniques , Recombinant Proteins/blood
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