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THE EFFECT OF INTRAVENOUS INFUSION TIME ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF THE SAME TOTAL DOSE OF AZOSEMIDE IN RABBITS
Author(s) -
PARK KWANG J.,
YOON WOO H.,
SHIN WAN G.,
LEE MYUNG G.
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199701)18:1<41::aid-bdd1>3.0.co;2-m
Subject(s) - pharmacokinetics , pharmacodynamics , pharmacology , medicine , intravenous infusions , anesthesia
The pharmacokinetics and pharmacodynamics of azosemide were evaluated after intravenous (IV) administration of the same total dose of azosemide, 1 mg kg −1 , in different infusion times, 1 min (treatment I) and 4 h (treatment II) to rabbits ( n =5, each). The loss of water and electrolytes in urine induced by azosemide was immediately replaced with infusion of equal volume of lactated Ringer's solution. Some pharmacokinetic parameters of azosemide were different between treatments I and II. For example, the mean value of terminal half‐life (70·5 versus 107 min), total body clearance (5·88 versus 8·32 mL min −1 kg −1 ), renal clearance (3·45 versus 6·51 mL min −1 kg −1 ), and mean residence time (18·5 versus 31·7 min) increased significantly in treatment II. The 8 h urine output (236 versus 733 mL) and 8 h urinary excretion of sodium (29·2 versus 76·4 mmol) and chloride (27·5 versus 78·9 mmol) increased significantly in treatment II although the total amount of 8 h urinary excretion of unchanged azosemide increased by only 15% in treatment II. This could be due to the fact that the urinary excretion rates of azosemide in treatment II remained for a longer period of time close to the maximally efficient urinary excretion rates of azosemide for both urine output and urinary excretion rates of sodium than in treatment I. Plasma concentrations of azosemide and hourly urine output and hourly urinary excretion of azosemide, sodium, potassium, and chloride during the apparent steady state (between 2 and 4 h) in treatment II were fairly constant. © 1997 by John Wiley & Sons, Ltd.