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Pharmacokinetic parameters of terbutaline in healthy man. An overview.

特布他林 药代动力学 分配量 化学 吸收(声学) 半衰期 口服 血浆浓度 分布(数学) 内分泌学 医学 药理学 内科学 材料科学 数学 数学分析 复合材料 哮喘
作者
Lars Nyberg
出处
期刊:PubMed 卷期号:134: 149-60 被引量:47
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After a single intravenous dose, plasma concentrations of terbutaline fall in a multi-exponential manner. The pharmacokinetic parameters are therefore preferably calculated by a non-compartmental method. Not until 6-12 h after an intravenous injection does terbutaline enter a mono-exponential decline phase. Negligence of this behaviour has produced reports of terminal half-lives in the literature, which are large underestimates. Prolonged sampling reveals that the terminal half-life of terbutaline in healthy subjects is about 17 h with an about twofold variation between subjects. This half-life determines, as a mean, about half the total area under the plasma concentration-time curve. Most studies have been performed in male subjects. On average, they have a body clearance of 3.0 mL/min/kg, 2/3 of this being the renal contribution. On a body weight basis, the renal clearance in women is at least as high as in men, possibly somewhat larger. Terbutaline's volume of distribution at steady state averages 1.6 L/kg. The systemic mean residence time of the drug is about 9 h. Terbutaline is little bound to plasma proteins but shows affinity to erythrocytes. However, clearance calculations should probably be based on the plasma concentration, because of a comparatively slow release rate from the erythrocytes. After oral administration, plasma concentration peaks of terbutaline appear within 1-4 h. Food reduces their height by about 40%. Particularly after single doses, more than one concentration peak is observed in plasma. Subjects differ considerably in their oral absorption capacity of the drug; an interindividual range of about 25-80% of the dose can be estimated. This creates a range in the extent of bioavailability of 7-26%, the decrease of the percentages being due to a high first-pass metabolism. There are strong indications that this occurs preferentially in the gut wall. The predominant metabolite of terbutaline formed in man is a sulphate conjugate. Mean bioavailability of oral terbutaline in fasting subjects is 14-15%. Food impairs the bioavailability by about one third because of reduced absorption. Despite the large variation in extent of terbutaline bioavailability between subjects, each individual behaves reproducibly from dose to dose.

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