Summary
The serum concentrations of α1-acid glycoprotein (AAG), albumin (HSA) and non-esterified fatty acids, and the serum binding of tertatolol were measured in four groups of individuals: healthy control subjects (n=24), and patients with inflammation (n=28), and hepatic (n=20) and renal (n=27) insufficiency.
Serum binding of tertatolol was increased in patients with inflammation (94.6%), decreased in patients with hepatic insufficiency (88.8%) and it was unchanged in patients with renal insufficiency (92.8%) as compared to controls (92.7%).
Multivariate analysis indicated that the changes were mainly related to concomitant changes in AAG concentration, which could account for 57% of intersubject variability in the bound/free ratio, and to a lesser extent in HSA, which accounted for only 4% of the variability in the binding.
The data show that the free fraction of the basic drug tertatolol in serum is affected by pathological conditions that cause changes in AAG concentration.
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Paillard F, Lanz B, Leviel F, Ardaillou R (1986) Renal hemodynamic effect of tertatolol in essential hypertension. Am J Nephrol 6 [Suppl 2]: 40–44
Beaufils M, Lanz B, Paillard F, Richet G (1986) Effects of tertatolol in hypertensive patients with chronic renal failure. Am J Nephrol 6 [Suppl 2]: 50–55
Campbell DB, Chignon JC, Devissaguet JPh (1986) Biodisposition of tertatolol in man: A review. Am J Nephrol [Suppl 2]: 61–68
Routledge PhA (1986) The plasma protein binding of basic drugs. Br J Clin Pharmacol 22: 499–506
Ståhle L, Wold S (1986) On the use of some multivariate statistical methods in pharmacological research. J Pharmacol Methods 16: 91–110
Müller WE (1986) Drug binding to human α1-acid glycoprotein. Focus on a single binding site. In: Tillement JP, Lindenlaub E (eds) Protein binding and drug transport. Schattauer, Stuttgart New York
Urien S (1986) Interaction of drugs with human plasma lipoproteins. In: Tillement JP, Lindenlaub E (eds) Protein binding and drug transport. Schattauer, Stuttgart New York
Reidenberg MM, Odar-Cederlöf I, von Bahr C, Borgå O, Sjöqvist F (1971) Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function. N Engl J Med 285: 264–267
Rudman D, Treadwell PE, Vogler WR, Howard CH, Hollins B (1972) An abnormal orosomucoid in the plasma of patients with neoplasic disease. Cancer Res 32: 1951–1959
Tinguely D, Baumann P, Conti M, Jonzier-Perey M, Schöpf J (1985) Interindividual differences in the binding of antide-pressives to plasma proteins: The role of the variants of α1-acid glycoprotein. Eur J Clin Pharmacol 27: 661–666
Abramson FP, Jenkins J, Ostchega Y (1982) Effects of cancer and its treatment on plasma concentration of α1-acid glycoprotein and propranolol binding. Clin Pharmacol Ther 32: 659–663
Sager G, Hansteen V, Aakesson I, Jacobsen S (1981) Effect of heparin on serum binding of propranolol in the acute phase of myocardial infarction. Br J Clin Pharmacol 12: 613–620
Belpaire FM, Braekman RA, Bogaert MG (1984) Binding of oxprenolol and propranolol to serum, albumin and α1-acid glycoprotein in man and other species. Biochem Pharmacol 33: 2065–2069
Piafsky KM, Borgå O, Odar-Cederlöf I, Johansson C, Sjöqvist F (1978) Increased plasma protein binding of propranolol and chlorpramazine mediated by disease-induced elevations of plasma α1-acid glycoprotein. N Engl J Med 299: 1435–1438
Baruzzi A, Contin M, Perucca E, Riva R (1986) Altered serum protein binding of carbamazepine in disease states associated with an increased α1-acid glycoprotein concentration. Eur J Clin Pharmacol 31: 85–89
Routledge PA, Lazar JD, Barchowsky A, Stargel WW, Wagner GS, Shand DG (1985) A free lignocaine index as a guide to unbound drug concentration. Br J Clin Pharmacol 20: 695–698
Barré J, Mallat A, Rosenbaum J, Deforges L, Houin G, Dhumeaux D, Tillement JP (1987) Pharmacokinetics of erythromycin in patients with severe cirrhosis. Respective influence of decreased serum binding and impaired liver metabolic capacity. Br J Clin Pharmacol 23: 753–757
Pedersen LE, Bonde J, Graudal NA, Backer NV, Hansen JES, Kampmann JP (1987) Quantitative and qualitative binding characteristics of disopyramide in serum from patients with decreased renal and hepatic function. Br J Clin Pharmacol 23: 41–46
Tiula E, Neuvonen PJ (1986) Effect of total drug concentration on the free fraction in uremic sera. Ther Drug Monitor 8: 27–31
Pearson RM (1977) Pharmacokinetics and response to diazoxide in renal failure. Clin Pharmacol 2: 198–204
McDevitt DG, Frisk-Holmberg M, Hollifield JW, Shand DG (1976) Plasma binding and the affinity of propranolol for a beta-receptor in man. Clin Pharmacol Ther 20: 152–157
Belpaire FM, Bogaert MG, Mugabo P, Rosseel MT (1986) Binding to serum α1-acid glycoprotein and effect of β-adrenoceptor antagonists in rats with inflammation. Br J Pharmacol 88: 697–705
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Urien, S., Morin, D., Renouard, A. et al. Variation in serum binding of tertatolol mediated by disease-induced modification of alpha-acid glycoprotein concentration. Eur J Clin Pharmacol 34, 381–385 (1988). https://doi.org/10.1007/BF00542440
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DOI: https://doi.org/10.1007/BF00542440