Abstract
A sandwich transfer enzyme immunoassay for salmon calcitonin (SCT) and its usability for the pharmacokinetic study are described. The assay procedure consisted of the reaction of SCT with 2,4‐dinitrophenyl biotinyl anti‐SCT IgG and anti‐SCT Fab′‐β‐D‐galactosidase conjugate, trapping onto (anti‐2,4‐dinitrophenyl bovine serum albumin) IgG‐coated polystyrene balls, eluting with ϵN‐2,4‐dinitrophenyl‐L‐lysine and transferring to streptavidin‐coated polystyrene balls and fluorometric detection of β‐D‐galactosidase activity. The practical detection limit of SCT was 0.05 pg (15 amol)/50 μl of sample and 1 pg/ml as the concentration. The application of this method has enabled us to directly estimate the bioavailability of SCT dosed intranasally at the therapeutic level (160 IU, 31 μg) for its anti‐osteoporotic effect as compared to an intramuscular dose (10 IU, 1.9 μg). The pharmacokinetic parameters of the intranasal SCT (n = 6) thus estimated were as follows: the area under the blood concentration‐time curve (AUC) = 9400 ± 5400 (SD) pg·h/ml, and the mean residence time (MRT) = 42 ± 14 (SD) min, when the AUC for the intramuscular SCT (n = 3) = 5600 ± 2000 (SD) pg·h/ml and the MRT = 39 ± 19 (SD) min. J. Clin. Lab. Anal. 11:380–387, 1997. © 1997 Wiley‐Liss, Inc.
No abstract.
Keywords: pharmacokinetics, osteoporosis, osteomalacia, thyroid, hormone
References
- 1. Chambers TJ, Magnus CJ: Calcitonin alters behavior of isolated osteoclasts. J Pathol 136: 27–39, 1982. [DOI] [PubMed] [Google Scholar]
- 2. Murrills RJ, Shane E, Lindsay R, Dempster DW: Bone resorption by isolated human osteoclasts in vitro: effects of calcitonin. J Bone Miner Res 4: 259–268, 1989. [DOI] [PubMed] [Google Scholar]
- 3. Nicholson GC, Moseley JM, Sexton PM, Mendelsohn FAO, Martin TJ: Abundant calcitonin receptors in isolated rat osteoclasts. J Clin Invest 78: 355–360, 1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Azria M: The Calcitonins: Physiology and Pharmacology. Karger, Basel, 1989. [Google Scholar]
- 5. Kohno T, Nakamuta H, Ichikawa M, Watabe K, Koida M: A noncompetitive enzyme immunoassay (hetero‐two‐site enzyme immunoassay) for salmon calcitonin: Determination of the bioavailability of subcutaneous salmon calcitonin and its correlation with the hypocalcemic activity in rats. J Clin Lab Anal 10: 91–97, 1996. [DOI] [PubMed] [Google Scholar]
- 6. Nakamuta H, Kohno T, Ichikawa M, Hoshino T, Watabe K, Koida M: Plasma level monitoring of nasal salmon calcitonin in the rats by a heterogeneous two‐site enzyme immunoassay. J Clin Lab Anal 11: 129–131, 1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Udenfriend S, Stein S, Bohlen P, Dairman W, Leimgruber W, Weigele M: Fluorescamine: A reagent for assay of amino acids, peptides, proteins, and primary amines in the picomole range. Science 178: 871–872, 1972. [DOI] [PubMed] [Google Scholar]
- 8. Hashida S, Ishikawa E: Detection of one milliattomole of ferritin by novel and ultrasensitive enzyme immunoassay. J Biochem 108: 960–964, 1990. [DOI] [PubMed] [Google Scholar]
- 9. Kohno T, Kitamura T, Tsuda K, Ishikawa E: Novel and sensitive enzyme immunoassay (immune‐complex‐transfer enzyme immunoassay) for alpha‐fetoprotein from hepatocellular carcinoma. J Clin Lab Anal 4: 183–188, 1990. [DOI] [PubMed] [Google Scholar]
- 10. Kohno T, Ishikawa E, Sugiyama S, Nakamura S: Novel enzyme immunoassay of anti‐insulin IgG in human serum. J Clin Lab Anal 2: 19–24, 1988. [Google Scholar]
- 11. Ishikawa E, Imagawa M, Hashida S, Yoshitake S, Hamaguchi Y, Ueno T: Enzyme‐labeling of antibodies and their fragments for enzyme immunoassay and immunohistochemical staining. J Immunoassay 4: 209–327, 1983. [DOI] [PubMed] [Google Scholar]
- 12. Kohno T, Ishikawa E: A highly sensitive enzyme immunoassay of antiinsulin antibodies in guinea pig serum. J Biochem 100: 1247–1251, 1986. [DOI] [PubMed] [Google Scholar]
- 13. Inoue S, Hashida S, Kohno T, Tanaka K, Ishikawa E: A micro‐scale method for the conjugation of affinity‐purified Fab′ to β‐D‐galactosidase from Escherichia coli J Biochem 98: 1387–1394, 1985. [DOI] [PubMed] [Google Scholar]
- 14. Ishikawa E, Kato K: Ultrasensitive enzyme immunoassay. Scand J Immunol 8(suppl. 7 ):43–55, 1978. [Google Scholar]
- 15. Tanaka K, Hashida S, Kohno T, Yamaguchi K, Ishikawa E: Novel and sensitive noncompetitive enzyme immunoassay to measure peptides by biotinylation. Anal Lett 22: 353–363, 1989. [Google Scholar]
- 16. Imagawa M, Hashida S, Ishikawa E, Mori H, Nakai C, Ichioka Y, Nakajima K: A highly sensitive sandwich enzyme immunoassay for insulin in human serum developed using capybara anti‐insulin Fab′‐ horseradish peroxidase conjugate. Anal Lett 16: 1509–1523, 1983. [Google Scholar]
- 17. Yamaoka K, Nakagawa T, Uno T: Statistical moments in pharmacokinetics. J Pharmacokin Biopharm 6: 547–558, 1978. [DOI] [PubMed] [Google Scholar]
- 18. Riegelman S, Collier P: The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. J Pharmacokin Biopharm 8: 509–534, 1980. [DOI] [PubMed] [Google Scholar]
- 19. Rong H, Deftos LJ, Ji H, Bucht E: Two‐site immunofluorometric assay of intact salmon calcitonin with improved sensitivity. Clin Chem 43: 71–75, 1997. [PubMed] [Google Scholar]
- 20. Kohno T, Misukawa T, Matsukura S, Ishikawa E: Sensitive time‐resolved fluorimetric immune‐complex‐transfer immunoassay for antithyroglobulin IgG in serum. J Clin Lab Anal 4: 224–230, 1990. [DOI] [PubMed] [Google Scholar]
- 21. Hashida S, Tanaka K, Inoue S, Hayakawa K, Ishikawa E: Time‐resolved fluorometric sandwich immunoassay for human growth hormone in serum and urine. J Clin Lab Anal 5: 38–42, 1991. [DOI] [PubMed] [Google Scholar]