Kolmogorov
Bluelighter
- Joined
- Nov 29, 2007
- Messages
- 24
Since the current price of amfonelic acid is prohibitive, decreasing the needed dosage by reducing hepatic metabolism could be useful.
Probenecid inhibits the renal clearance and renal glucuronidation of nalidixic acid
Abstract The aim of this pilot study was to demonstrate the possible inhibitory effect of probenecid on the renal glucuronidation and on the renal clearance of nalidixic acid in a human volunteer. Under acidic urine conditions, hardly any nalidixic acid is excreted unchanged ( 0.2% ). It is excreted as acyl glucuronide ( 53.4% ) , 7-hydroxymethylnalidixic acid ( 10.0% ), the latter's acyl glucuronide 30.9%, and 7-carboxynalidixic acid ( 4.2% ). Under probenecid co-medication the renal glucuronidation of nalidixic acid is reduced from 53% to 16%; the renal clearance of both nalidixic acid and 7-hydroxymethylnalidixic acid are reduced (p <0.001); the intrinsict 1/2 of the metabolite 7-hydroxymethylnalidixic acid increased from 0.48 h to 4.24 h. The amount of acyl glucuronidation of 7-hydroxymethylnalidixic acid was not altered. Thein vitro protein binding of both acyl glucuronides was increased, while no effect on the unconjugated compounds was seen. Nalidixic acid had no effect on the maximal renal excretion rate of probenecid acyl glucuronide.
T. B. Vree1, M. Van den Biggelaar-Martea1, E. W. J. Van Ewijk-Beneken Kolmer1 and Y. A. Hekster
Since the only difference between nalidixic acid and amfonelic acid is a benzene ring, and the carboxylic acid site of glucuronidation is the same, I believe that probenecid should inhibit that reaction too.
By the way, I was looking at that metabolite of nalidixic acid, 7-hydroxynalidixic acid. Could it be a precursor to AA?
Probenecid inhibits the renal clearance and renal glucuronidation of nalidixic acid
Abstract The aim of this pilot study was to demonstrate the possible inhibitory effect of probenecid on the renal glucuronidation and on the renal clearance of nalidixic acid in a human volunteer. Under acidic urine conditions, hardly any nalidixic acid is excreted unchanged ( 0.2% ). It is excreted as acyl glucuronide ( 53.4% ) , 7-hydroxymethylnalidixic acid ( 10.0% ), the latter's acyl glucuronide 30.9%, and 7-carboxynalidixic acid ( 4.2% ). Under probenecid co-medication the renal glucuronidation of nalidixic acid is reduced from 53% to 16%; the renal clearance of both nalidixic acid and 7-hydroxymethylnalidixic acid are reduced (p <0.001); the intrinsict 1/2 of the metabolite 7-hydroxymethylnalidixic acid increased from 0.48 h to 4.24 h. The amount of acyl glucuronidation of 7-hydroxymethylnalidixic acid was not altered. Thein vitro protein binding of both acyl glucuronides was increased, while no effect on the unconjugated compounds was seen. Nalidixic acid had no effect on the maximal renal excretion rate of probenecid acyl glucuronide.
T. B. Vree1, M. Van den Biggelaar-Martea1, E. W. J. Van Ewijk-Beneken Kolmer1 and Y. A. Hekster
Since the only difference between nalidixic acid and amfonelic acid is a benzene ring, and the carboxylic acid site of glucuronidation is the same, I believe that probenecid should inhibit that reaction too.
By the way, I was looking at that metabolite of nalidixic acid, 7-hydroxynalidixic acid. Could it be a precursor to AA?
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