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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Half-Life

  • Using a quantitative micro-culture assay, we demonstrate here that the latent reservoir decays with a mean half-life of 6.3 months in patients who consistently maintain plasma HIV-1 RNA levels of fewer than 50 copies/ml [1].
  • Attempts to use SRIF as an adjunct in the treatment of diabetes mellitus met with limited success due to its short biological half-life and the undesirable diabetogenic activity of its insulin-lowering properties [2].
  • 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% [3].
  • In addition, results from animal studies show that this chimeric Factor IX, when infused into a dog with hemophilia B, exhibits a greater than threefold increase in clotting activity, and has a biological half-life equivalent to recombinant wild-type Factor IX [4].
  • Using the plasma disappearance rate of antipyrine (15 mg per kg of body weight) as an index of liver microsomal metabolism, a significant decrease in the half-life of antipyrine has been observed: 11.7 +/- (1 sd) 4.7 hr before treatment as compared to 6.9 +/- 2.3 hr on the 7th day [5].

Psychiatry related information on Half-Life


High impact information on Half-Life

  • Thus, it is now possible to engineer IgGs with altered affinities for FcRn, and this has relevance to the modulation of IgG serum half-life and maternofetal IgG transport for therapeutic applications [11].
  • Increases in p53 protein levels after DNA damage have largely been attributed to an increase in the half-life of p53 protein [12].
  • Unexpectedly, this effect is attributed to a small but significant inhibition of p21 translation combined with its short half-life [13].
  • To address the biological importance of Hes7 instability, we generated mice expressing mutant Hes7 with a longer half-life (approximately 30 min compared with approximately 22 min for wild-type Hes7) but normal repressor activity [14].
  • During treatment, methanol had an elimination half-life of 54 hours [15].

Chemical compound and disease context of Half-Life


Biological context of Half-Life


Anatomical context of Half-Life


Associations of Half-Life with chemical compounds

  • In agreement with this model, tubulin message is found to be short-lived and has an approximately 2 hr half-life in cells treated with actinomycin D [31].
  • There was no correlation between any laboratory test of liver function and the plasma theophylline half-life, except for serum albumin (r = 0.92, P less than 0.001) [32].
  • From measurements of the rate of decline in 125I-LDL binding activity after administration of cycloheximide, the LDL receptor was calculated to have a half-life of about 25 hr [33].
  • An inverse correlation was found between plasma half-life of the drug and creatinine clearance (r = 0.68, P less than 0.01) [34].
  • Cimetidine is known to impair the hepatic microsomal oxidation of diazepam, reducing its clearance and prolonging its half-life [35].

Gene context of Half-Life

  • Protein synthesis inhibition by cycloheximide (CHX) treatment indicated that the half-life of p21/SDI-1 in dividing HT1 cells was approximately 30 min [36].
  • The half-life of the HIF-1alpha subunit is determined by oxygen-dependent prolyl hydroxylation, which is required for binding of the von Hippel-Lindau protein (VHL), the recognition component of an E3 ubiquitin ligase that targets HIF-1alpha for ubiquitination and degradation [37].
  • IFN-alpha may produce these effects by shortening the half-life of cytokine mRNA, since TNF mRNA half-life in B-CLL and HCL cells is substantially reduced when the cells are cultured with IFN-alpha [38].
  • IL-4 elevated P-selectin mRNA by increasing its transcription rate rather than by prolonging its already long half-life [39].
  • Indeed, the half-life of IL-1ra mRNA was prolonged in PMN stimulated in the presence of IL-10 and LPS, as compared with cells stimulated with LPS alone [40].

Analytical, diagnostic and therapeutic context of Half-Life


  1. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Ramratnam, B., Mittler, J.E., Zhang, L., Boden, D., Hurley, A., Fang, F., Macken, C.A., Perelson, A.S., Markowitz, M., Ho, D.D. Nat. Med. (2000) [Pubmed]
  2. Luteinising hormone-releasing and anti-fertility properties of a glucagon-selective somatostatin analogue. Bex, F.J., Corbin, A., Sarantakis, D., Lien, E. Nature (1980) [Pubmed]
  3. Metabolic clearance of recombinant human growth hormone in health and chronic renal failure. Haffner, D., Schaefer, F., Girard, J., Ritz, E., Mehls, O. J. Clin. Invest. (1994) [Pubmed]
  4. Replacing the first epidermal growth factor-like domain of factor IX with that of factor VII enhances activity in vitro and in canine hemophilia B. Chang, J.Y., Monroe, D.M., Stafford, D.W., Brinkhous, K.M., Roberts, H.R. J. Clin. Invest. (1997) [Pubmed]
  5. Induction of hepatic microsomal enzymes after brief administration of rifampicin in man. Miguet, J.P., Mavier, P., Soussy, C.J., Dhumeaux, D. Gastroenterology (1977) [Pubmed]
  6. Brain elimination half-life of fluvoxamine measured by 19F magnetic resonance spectroscopy. Strauss, W.L., Layton, M.E., Dager, S.R. The American journal of psychiatry. (1998) [Pubmed]
  7. Rebound insomnia: a critical review. Gillin, J.C., Spinweber, C.L., Johnson, L.C. Journal of clinical psychopharmacology. (1989) [Pubmed]
  8. Carbohydrate-deficient transferrin in serum: a new marker of potentially harmful alcohol consumption reviewed. Stibler, H. Clin. Chem. (1991) [Pubmed]
  9. Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites in human samples including the catechol-type metabolite (3,4-dihydroxymethamphetamine). Pizarro, N., Farré, M., Pujadas, M., Peiró, A.M., Roset, P.N., Joglar, J., de la Torre, R. Drug Metab. Dispos. (2004) [Pubmed]
  10. Pharmacokinetics of pimozide in adults and children with Tourette's syndrome. Sallee, F.R., Pollock, B.G., Stiller, R.L., Stull, S., Everett, G., Perel, J.M. Journal of clinical pharmacology. (1987) [Pubmed]
  11. Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Ghetie, V., Ward, E.S. Annu. Rev. Immunol. (2000) [Pubmed]
  12. Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Takagi, M., Absalon, M.J., McLure, K.G., Kastan, M.B. Cell (2005) [Pubmed]
  13. The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Beuvink, I., Boulay, A., Fumagalli, S., Zilbermann, F., Ruetz, S., O'Reilly, T., Natt, F., Hall, J., Lane, H.A., Thomas, G. Cell (2005) [Pubmed]
  14. Instability of Hes7 protein is crucial for the somite segmentation clock. Hirata, H., Bessho, Y., Kokubu, H., Masamizu, Y., Yamada, S., Lewis, J., Kageyama, R. Nat. Genet. (2004) [Pubmed]
  15. Fomepizole for the treatment of methanol poisoning. Brent, J., McMartin, K., Phillips, S., Aaron, C., Kulig, K. N. Engl. J. Med. (2001) [Pubmed]
  16. Drug metabolism in liver disease. Identification of patients with impaired hepatic drug metabolism. Farrell, G.C., Cooksley, W.G., Hart, P., Powell, L.W. Gastroenterology (1978) [Pubmed]
  17. Heparin kinetics in venous thrombosis and pulmonary embolism. Hirsh, J., van Aken, W.G., Gallus, A.S., Dollery, C.T., Cade, J.F., Yung, W.L. Circulation (1976) [Pubmed]
  18. Prostaglandin I2 half-life regulated by high density lipoprotein is decreased in acute myocardial infarction and unstable angina pectoris. Aoyama, T., Yui, Y., Morishita, H., Kawai, C. Circulation (1990) [Pubmed]
  19. In vitro synthesis of the tryptophan operon leader peptides of Escherichia coli, Serratia marcescens, and Salmonella typhimurium. Das, A., Urbanowski, J., Weissbach, H., Nestor, J., Yanofsky, C. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  20. Competitive binding radioassay for 5-fluorodeoxyuridine 5'-monophosphate in tissues. Murinson, D.S., Anderson, T., Schwartz, H.S., Myers, C.E., Chabner, B.A. Cancer Res. (1979) [Pubmed]
  21. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Lee, S., Elenbaas, B., Levine, A., Griffith, J. Cell (1995) [Pubmed]
  22. 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. A phase I trial. Lambert, J.S., Seidlin, M., Reichman, R.C., Plank, C.S., Laverty, M., Morse, G.D., Knupp, C., McLaren, C., Pettinelli, C., Valentine, F.T. N. Engl. J. Med. (1990) [Pubmed]
  23. Equine chorionic gonadotropin. Murphy, B.D., Martinuk, S.D. Endocr. Rev. (1991) [Pubmed]
  24. JNK targets p53 ubiquitination and degradation in nonstressed cells. Fuchs, S.Y., Adler, V., Buschmann, T., Yin, Z., Wu, X., Jones, S.N., Ronai, Z. Genes Dev. (1998) [Pubmed]
  25. RNase E autoregulates its synthesis by controlling the degradation rate of its own mRNA in Escherichia coli: unusual sensitivity of the rne transcript to RNase E activity. Jain, C., Belasco, J.G. Genes Dev. (1995) [Pubmed]
  26. Translation of Xenopus liver messenger RNA in Xenopus oocytes: vitellogenin synthesis and conversion to yolk platelet proteins. Berridge, M.V., Lane, C.D. Cell (1976) [Pubmed]
  27. Genetic ablation and restoration of the olfactory topographic map. Gogos, J.A., Osborne, J., Nemes, A., Mendelsohn, M., Axel, R. Cell (2000) [Pubmed]
  28. Metabolic stabilization of endplate acetylcholine receptors regulated by Ca2+ influx associated with muscle activity. Rotzler, S., Schramek, H., Brenner, H.R. Nature (1991) [Pubmed]
  29. Disposition and pharmacodynamics of methamphetamine in pregnant sheep. Burchfield, D.J., Lucas, V.W., Abrams, R.M., Miller, R.L., DeVane, C.L. JAMA (1991) [Pubmed]
  30. The effect of graft-versus-host disease on T cell production and homeostasis. Dulude, G., Roy, D.C., Perreault, C. J. Exp. Med. (1999) [Pubmed]
  31. Mechanisms of regulating tubulin synthesis in cultured mammalian cells. Ben-Ze'ev, A., Farmer, S.R., Penman, S. Cell (1979) [Pubmed]
  32. Theophylline disposition in patients with hepatic cirrhosis. Piafsky, K.M., Sitar, D.S., Rangno, R.E., Ogilvie, R.I. N. Engl. J. Med. (1977) [Pubmed]
  33. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Brown, M.S., Goldstein, J.L. Cell (1975) [Pubmed]
  34. Increased glomerular filtration rate in patients with major burns and its effect on the pharmacokinetics of tobramycin. Loirat, P., Rohan, J., Baillet, A., Beaufils, F., David, R., Chapman, A. N. Engl. J. Med. (1978) [Pubmed]
  35. Clinical importance of the interaction of diazepam and cimetidine. Greenblatt, D.J., Abernethy, D.R., Morse, D.S., Harmatz, J.S., Shader, R.I. N. Engl. J. Med. (1984) [Pubmed]
  36. CCAAT/enhancer-binding protein alpha (C/EBP alpha) inhibits cell proliferation through the p21 (WAF-1/CIP-1/SDI-1) protein. Timchenko, N.A., Wilde, M., Nakanishi, M., Smith, J.R., Darlington, G.J. Genes Dev. (1996) [Pubmed]
  37. OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha. Baek, J.H., Mahon, P.C., Oh, J., Kelly, B., Krishnamachary, B., Pearson, M., Chan, D.A., Giaccia, A.J., Semenza, G.L. Mol. Cell (2005) [Pubmed]
  38. Effects of interferon alpha on autocrine growth factor loops in B lymphoproliferative disorders. Heslop, H.E., Bianchi, A.C., Cordingley, F.T., Turner, M., Chandima, W., De Mel, C.P., Hoffbrand, A.V., Brenner, M.K. J. Exp. Med. (1990) [Pubmed]
  39. Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells. Yao, L., Pan, J., Setiadi, H., Patel, K.D., McEver, R.P. J. Exp. Med. (1996) [Pubmed]
  40. Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. Cassatella, M.A., Meda, L., Gasperini, S., Calzetti, F., Bonora, S. J. Exp. Med. (1994) [Pubmed]
  41. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. Stamey, T.A., Yang, N., Hay, A.R., McNeal, J.E., Freiha, F.S., Redwine, E. N. Engl. J. Med. (1987) [Pubmed]
  42. Removal of phenytoin by hemodialysis in uremic patients. Martin, E., Gambertoglio, J.G., Adler, D.S., Tozer, T.N., Roman, L.A., Grausz, H. JAMA (1977) [Pubmed]
  43. Role of the kidneys in the metabolism of plasma mevalonate. Studies in humans and in rhesus monkeys. McNamara, D.J., Ahrens, E.H., Parker, T.S., Morrissey, K. J. Clin. Invest. (1985) [Pubmed]
  44. Phase II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors. Motzer, R.J., Mazumdar, M., Gulati, S.C., Bajorin, D.F., Lyn, P., Vlamis, V., Bosl, G.J. J. Natl. Cancer Inst. (1993) [Pubmed]
  45. Efficacy of treatment with the iron (III) complex of diethylenetriamine pentaacetic acid in mice and primates inoculated with live lethal dose 100 Escherichia coli. Molina, L., Studenberg, S., Wolberg, G., Kazmierski, W., Wilson, J., Tadepalli, A., Chang, A.C., Kosanke, S., Hinshaw, L. J. Clin. Invest. (1996) [Pubmed]
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