PROPRANOLOL IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS .2. DISPOSITION AFTER SUBCUTANEOUS AND INTRACEREBROVENTRICULAR ADMINISTRATION

被引:23
作者
SMITS, JFM
STRUYKERBOUDIER, HAJ
机构
[1] Department of Pharmacology, Rijksuniversiteit Limburg, Maastricht, NL-6200 MD
关键词
Intracerebroventricular injection; Pharmacokinetics; Propranolol; Spontaneously hypertensive rats; Subcutaneous injection;
D O I
10.1007/BF00498752
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The disposition of dl-propranolol was studied in spontaneously hypertensive rats (SHR), both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injection of 1 mg/kg. 1. Upon s.c. injection propranolol appeared rapidly in plasma. A maximum concentration of 374 ± 33 ng/ml (N=10) was reached 5 min after injection. After a distribution phase with a half-life of t1/2α=17 min propranolol was eliminated with a t1/2β=59 min. 2. Both propranolol and its metabolites were taken up rapidly into all tissues studied. Highest concentrations (10.4±1.5 μg/g, N=5) were found in lungs 30 min after injection. 3. Neither propranolol nor its metabolites accumulated in any of the tissues examined. 4. Upon i.c.v. injection of propranolol, a maximal concentration of 573±47 ng/ml (N=3) was reached in plasma already 2 min after injection. In this case t1/2α was 13 min and t1/2β was 80 min. 5. Dialysis experiments indicated that propranolol is bound to plasma proteins for 92% in the concentration range of 20-100 ng/ml. With increasing concentrations binding diminishes progressively. At the highest concentration tested (345 ng/ml) only 76% was bound. It is concluded that s.c. and i.c.v. injection of an identical dose of propranolol gives a similar plasma concentration-time profile. Moreover, it is suggested that the pharmacokinetic behaviour of propranolol in SHR does not explain the delayed antihypertensive effect of this drug. © 1979 Springer-Verlag.
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页码:19 / 24
页数:6
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