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- W56804776 abstract "The clinical pharmacokinetics and pharmacokinetic/dynamic properties of the beta-adrenergic drugs fenoterol, salbutamol and terbutaline are reviewed. Sulfate conjugates are the main metabolites in man. The protein binding of these derivatives is rather weak with most pronounced binding observed e.g. fenoterol (40%). Disposition after parenteral administration shows a multi-exponential behavior for all the substances with linear but also stereo-selective pharmacokinetics. After parenteral administration, the drugs are mainly eliminated by renal processes while after oral administration a pronounced metabolic clearance (high first pass effect) is responsible for a low bioavailability, especially for fenoterol (2%). The total clearance for fenoterol is about twice that of salbutamol and terbutaline. Seven to 15% of the delivered aerosol reach typically the systemic circulation. In patients with respiratory disorders, pulmonary absorption is however highly dependent on the disease state. Pharmacokinetics in children do not significantly differ from adults when expressed per kg body weight. Patients with renal failure but not asthmatics show changed pharmacokinetic profiles. Only insignificant interactions with other drugs have been found. Pharmacokinetic/dynamic modeling approaches indicated that fenoterol is 25 times more active at the site of action than salbutamol and terbutaline, but all three drugs show similar bronchopulmonary selectivities. When the overall clinical activity, determined by pharmacokinetic and dynamic properties is compared, the activity gap is reduced: fenoterol (8) greater than salbutamol (2) greater than terbutaline (1). Differences in the first pass effect even inverse the pattern after oral administration. PK/PD modeling quantified the pulmonary effect after inhalation and suggested that the higher incidence of side effects for fenoterol might be linked to an overdosing problem. The application of PK/PD principles may improve the clinical usage and therapy of beta-2-adrenergic drugs." @default.
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- W56804776 date "1992-09-01" @default.
- W56804776 modified "2023-09-23" @default.
- W56804776 title "Pharmacokinetic/pharmacodynamic characteristics of the beta-2-agonists terbutaline, salbutamol and fenoterol." @default.
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