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Pharmacokinetics and pharmacodynamics of bumetanide after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt induced hypertensive rats. 1993

K S Han, and S H Lee, and M G Lee, and N D Kim
College of Pharmacy, Seoul National University, Korea.

The pharmacokinetics and pharmacodynamics of bumetanide were investigated after intravenous (i.v.) administration, 10 mg kg-1, and oral administration, 20 mg kg-1, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate-salt induced hypertensive rats (DOCA-salt rats). After i.v. administration, the pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between SHRs and the control Wistar rats. Similar results were also shown between DOCA-salt rats and the control Sprague-Dawley (SD) rats. After oral administration, the AUC0-12 h decreased significantly (186 versus 335 micrograms min ml-1) in SHRs and this resulted in decreased F(15.4 versus 23.6 and 2.78 versus 5.76% using two equations) in SHRs when compared with the control Wistar rats, although none of the other pharmacokinetic parameters varied significantly between SHRs and Wistar rats. This effect seemed to be due to the decreased enterohepatic recirculation of bumetanide in SHRs: the amounts of both bumetanide and its glucuronide product, which are capable of enterohepatic recirculation, excreted in 8 h bile juice decreased significantly in SHRs (11.3 versus 37.4 micrograms as expressed in terms of bumetanide) when compared with Wistar rats. The pharmacodynamic parameters did not vary significantly between SHRs and Wistar rats after oral administration of bumetanide. The pharmacokinetic and pharmacodynamic parameters of bumetanide did not vary significantly between DOCA-salt rats and SD rats after oral administration of the drug. The liver weights compared to body weight increased significantly in SHRs when compared with Wistar rats and the corresponding values for the kidney increased significantly in DOCA-salt rats when compared with SD rats.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002034 Bumetanide A sulfamyl diuretic. Bumedyl,Bumethanide,Bumex,Burinex,Drenural,Fordiuran,Miccil,PF-1593,PF 1593,PF1593
D003900 Desoxycorticosterone A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE 21-Hydroxyprogesterone,Cortexone,Deoxycorticosterone,Desoxycortone,11-Decorticosterone,21-Hydroxy-4-pregnene-3,20-dione,11 Decorticosterone,21 Hydroxy 4 pregnene 3,20 dione,21 Hydroxyprogesterone
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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