A-l-Acid glycoprotein

The biotransformation (468-470)and clinical pharmacokinetics (471) of olanzapine have been investigated extensively. The drug exhibits dose proportional linear pharmacokinetics in therapeutic dose ranges (471). Olanzapine is bound to both albumin and a-l-acid glycoproteins in the plasma. The mean elimination half-life in healthy adults was 33 h and the plasma clearance averaged 26 L/h. 

Several demographic variables were collected however, weight, ethnic origin, and a-l-acid glycoprotein (AAG) were considered the more likely covariates to influence pharmacokinetics, based on previous data (15). A summary of demographics in actual data obtained for each study is given in Table 16.2. 

O Keeffe, D. H., Ebel, R. E., and Peterson, J. A. (1978). Studies of the oxygen binding site of cytochrome P-450. Nitric oxide as a spin-label probe. /. Biol. Chem. 253, 3509-3516. Pous, C., Giroud, J. P., Damais, C., Raichvarg, D., and Chauvelot-Moachon, L. (1990). Effect of recombinant human interleukin-1 and tumor necrosis factor a on liver cytochrome P-450 and serum a-l-acid glycoprotein concentrations in the rat. Drug Metab. Dispos. 18, 467-470. 

Eap CB, Bauman P (1989) The generic polymorphism of human a-l-acid glycoprotein genetics, biochemistry, physiological functions and pharmacology. Prog Clin Biol Res 300 ... 

Lacunza, I. and de Frutos, M., Different capillary isoelectric focusing approaches for analysis of a-l-acid glycoprotein, PACE Setter, 10,5, 2006. 

Imre, T., Schlosser, G., Pocsfalvi, G., Sicihano, R., Mobiar-SzoUosi, E., Kremmer, T., Malorni, A., and Vekey, K., Glycosylation site analysis of human alpha-l-acid glycoprotein (AGP) by capillary liquid chromatography-electrospray mass spectrometry. Journal of Mass Spectrometry 40(11), 1472-1483, 2005. 

Dente, L., Pizza, M.G., Metspalu, A. and Cortese, R. (1987) Structure and expression of the genes coding for human a i -acid glycoprotein. EMBO Journal 6,2289-2296. 

P. van der Sluijs and D. K. F. Meijer, Binding of drugs with a quaternary ammonium group to alpha-l-acid glycoprotein, /. Pharmacol. Exp. Then, 234 703 (1985). 

B. M. Sadler, C. Gillotin, Y. Lou, and D. S. Stein, In vivo effect of alpha-l-acid glycoprotein on pharmacokinetics of amprenavir, a human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 45 852-856 (2001). 

Jorgensen, H. G., Elliott, M. A., Allan, E. K., Carr, C. E., Holyoake, T. L., Smith, K. D, 2002, a 1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI57 Blood. 99, 713-715. Jullien, M., Garel, J-R., Merola, F. and Brochon J-C, 1986, Quenching by acrylamide and temperature of a fluorescent probe attached to the active site of ribonuclease. European Biophysical Journal 13, 131-137... 

The lidocaine/cimetidine interaction is well studied but controversial. It is confused by the differences between the studies (healthy subjects, patients with different diseases, different modes of drug administration, etc). A fall in the clearance of lidoeaine (15% or more) and a resultant rise in the serum levels should be looked for if eimetidine is used, but a clinically significant alteration may not occur in every patient. It may possibly be of less importance in patients following a myocardial infarction because of the increased amounts of alpha-l-acid glycoprotein, which alters the levels of bound and free lidoeaine. Monitor all patients closely for evidence of toxicity and, where possible, check serum lidoeaine levels regularly. A reduced infusion rate may be needed. Ranitidine would appear to be a suitable alternative to eimetidine. See also Anaesthetics, local -i- H2-receptor antagonists , p.l 11. 

The reduced lidocaine serum levels are possibly due to liver enzyme induction when lidocaine is given orally the marked reduction in levels results from the stimulation of hepatic first-pass metabolism by phenytoin. In addition, patients taking antiepileptics including phenytoin had higher plasma concentrations ofalpha-l-acid glycoprotein, which may result in a lower free fraction of lidocaine in the plasma. ... 

Albumin alpha(l)-acid glycoprotein Albumin lysozyme ribonuclease a Amyloid precursor protein Beta lactoglobulin Botulinum neurotoxin Erythropoietin Erythropoietin Hemoglobin variants, mouse Hemoglobin variants, human Hemoglobin, globin chains HIV-1 reverse transcriptase Insulin trypsin... 

Ceciliani, E, V. Pocacqua,A.Miianda-Ribera, V. Bronzo, C. Lecchi and P. Sartorelli, 2007. Alpha(l)-acid glycoprotein modulates apoptosis in bovine monocytes. Vet Immunol. Immimopathol. 116 (3-4), 145-152. 

Fitos, L Visy, J. Zsila, F. Bikadi, Z. Mady, G. Simonyi, M. Specific ligand binding on genetic variants of human a 1-acid glycoprotein studied... 

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

Oral mucosae are covered with mucus which serves as a link between the adhesive and the membrane. Mucus is a glycoprotein consisting of a large peptide backbone with pendant oligosaccharide side chains. The side chains terminate in sialic or sulfonic acids, L-fucose, sulfated galactose, or A -acetylglucosamine. The glycoprotein component imparts the viscous or gel-like (non-Newtonian) nature due to its capacity... 

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