Effects of furosemide on the plasma and urinary concentrations and the excretion of fentanyl: model for the study of drug interaction in the horse.

The effects of furosemide (0.55 mg/kg IV) on the plasma and urinary fentanyl (PFE UFE) concentrations were studied during steady-state conditions. The PFE during the steady-state period was 0.31 +/- 0.027 ng/ml, with no significant changes occurring, even though the rate of excretion of fentanyl (EX) increased during the 1st hour from 112.0 +/- 21.6 to 534.5 +/- 82.9 ng/minute. The EX returned to control levels within 3 hours, as did the UFE. The injection of furosemide increased glomerular filtration rate from 1.97 +/- 0.21 to 3.81 +/- 0.75 ml/kg/min. The fractional reabsorption decreased from a control of 70.3 +/- 6.2% to 25.2 +/- 2.3% during the 1st hour, returning to control levels at 3 hours after furosemide was given. The total body clearance of fentanyl increased slightly during the peak period of diuresis. The return of EX, fractional reabsorption, UFE, and clearance of endogenous creatinine to control levels occurred before the return of urine specific gravity, indicating the ability of the kidney to concentrate fentanyl before its water concentrating capacity had returned.