Alternating sequential dosing with furosemide and ethacrynic acid in drug tolerance in the newborn
S. Chemtob, J. L. Doray, N. Laudignon, A. Papageorgiou, D. R. Varma and J. V. Aranda
Department of Neonatal Research and Development Pharmacology and Therapeutics, Montreal Children's Hospital, Quebec, Canada.
Drug tolerance seems to develop rapidly after the administration of
sequential doses of the same loop diuretic. We evaluated whether
alternating different loop diuretics could achieve the same initial
diuretic response in the newborn. In a randomized double crossover study,
we examined the diuretic and saliuretic effects of alternating doses of
furosemide and ethacrynic acid (1 mg/kg administered intravenously every 24
hours) in 10 newborns, who received the drugs in the following sequential
order: (1) furosemide, (2) ethacrynic acid, and (3) furosemide (group 1, n
= 5); and (1) ethacrynic acid (2) furosemide, and (3) ethacrynic acid
(group 2, n = 5). Hourly urine specimens were collected for the
determination of rates of urinary and fractional excretion of sodium,
chloride, and potassium and of urinary flow, before and 6 hours after
dosing. There were no differences between the groups at each dose for all
parameters measured. A significant decrease in prediuretic and postdiuretic
rates of urinary flow, in sodium and chloride excretion, and in the
fractional excretion of these electrolytes was observed before and after
dosing. The associated reduction in patients' weights suggested a depletion
in plasma volume. In conclusion, consecutive alternation of furosemide and
ethacrynic acid in the same newborn does not prevent the development of
pharmacologic tolerance to loop diuretics, since diuresis, natriuresis, and
chloriuresis decrease after successive sequential administration of these
drugs.
