Pharmacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum.
The pharmacokinetics and pharmacodynamics of furosemide were compared after an oral administration or a direct administration of Lasix into the duodenum in humans (40 mg). Furosemide was absorbed quickly after a direct administration of Lasix into the duodenum; the peak plasma concentration of furosemide was reached within 1 h in both routes of administration, and the peak concentration was higher in all four subjects after a direct administration into the duodenum than after an oral administration. Furosemide was absorbed considerably after a direct administration of Lasix into the duodenum; the values of the area under the plasma concentration-time curves of furosemide from time zero to 4 h (AUC0-4 h, 93.6 versus 122 micrograms min mL-1, p < 0.123) and the cumulative amounts of the dose excreted in 8 h (10,600 versus 15,000 micrograms, p < 0.0185) and 24 h (11,300 versus 15,400 micrograms, p < 0.0192) urine as unchanged furosemide were significantly higher after a direct administration into the duodenum than after an oral administration. However, the amounts excreted in urine as glucuronide conjugates, a metabolite of furosemide, tended to increase after an oral administration (4030 versus 1670 micrograms as expressed in terms of furosemide, p < 0.0858) when compared to a direct administration into the duodenum, possibly due to the increased gastric first-pass metabolism of furosemide. The 8 h urine output and 8 h urinary excretion of sodium did not increase significantly after a direct administration of Lasix into the duodenum, despite the significantly greater amount of the drug delivered to the active site after a direct administration into the duodenum. This could be explained by the fact that the urinary excretion rates of furosemide after a direct administration into the stomach were closer to the values of maximally efficient urinary excretion rate of furosemide during the 8 h experimental period than after a direct administration into the duodenum.
Lee
W I
WI
College of Pharmacy, Seoul National University, Kwanak-Gu, Korea.
Yoon
W H
WH
Shin
W G
WG
Song
I S
IS
Lee
M G
MG
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D004232:Diuretics / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D005665:Furosemide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000652:urine; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D004232:Diuretics; D005665:Furosemide; D012964:Sodium