RT Journal Article
SR Electronic
T1 Renal excretion of famotidine and role of adenosine in renal failure induced by bacterial lipopolysaccharide in rats.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 8
OP 13
VO 22
IS 1
A1 T Hasegawa
A1 M Nadai
A1 L Wang
A1 Y Takayama
A1 K Kato
A1 T Nabeshima
A1 N Kato
YR 1994
UL http://dmd.aspetjournals.org/content/22/1/8.abstract
AB Our previous studies have reported that bacterial lipopolysaccharide (LPS) dramatically changes the ability of the active tubular anion secretory system in rats. The present study has investigated the effects of LPS on the pharmacokinetics and renal handling of famotidine, an organic cation drug excreted primarily by an active tubular secretion mechanism in rats. The role of adenosine in the LPS-induced renal failure was also investigated using theophylline, an adenosine antagonist. Pretreatment with LPS (250 micrograms/kg) significantly decreased the steady-state volume of distribution, systemic clearance, and renal clearance (CLr) of famotidine, but not nonrenal clearance. No significant differences in total urinary recovery of unchanged famotidine were observed between treatments. Pretreatment with LPS significantly decreased the glomerular filtration rate (GFR), estimated as inulin clearance. LPS increased the clearance ratio of famotidine (CLr/GFR), but not the net tubular secretion, indicating that LPS has little or no effect on the active tubular cation secretory system. Theophylline (10 mg/kg) improved LPS-induced decrease in GFR without causing any changes in the pharmacokinetic parameters of famotidine. These findings provide further evidence that LPS produces different effects on the distribution and the active tubular secretory systems of anion and cation drugs, and that adenosine may play an important role in the induction of renal failure by LPS.