indication

For the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species.

pharmacology

Nalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor.

mechanism of action

Evidence exists for Nalidixic acid that its active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis.

toxicity

ORAL (LD₅₀): Acute: 1160 mg/kg [Rat]. 572 mg/kg [Mouse]. Toxic psychosis, convulsions, increased intracranial pressure, or metabolic acidosis may occur in patients taking more than the recommended dosage. Vomiting, nausea, and lethargy may also occur following overdosage.

biotransformation

Hepatic. 30% of administered dose is metabolized to the active metabolite, hydroxynalidixic acid. Rapid conjugation of parent drug and active metabolite to inactive metabolites. Metabolism may vary widely among individuals. In the urine, hydroxynalidixic acid represents 80 to 85% of the antibacterial activity.

absorption

Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.

half life

1.1 to 2.5 hours in healthy adult patients, and up to 21 hours in patients with impaired renal function.

route of elimination

Following oral administration, NegGram is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys. Approximately four percent of NegGram is excreted in the feces.

drug interactions

Acenocoumarol: The quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of acenocoumarol.

Anisindione: The quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of anisindione.

Calcium Acetate: Calcium salts such as calcium acetate may decrease the absorption of quinolone antibiotics such as nalidixic acid. Of concern only with oral administration of both agents. Interactions can be minimized by administering oral quinolone at least 2 hours before, or 6 hours after, the dose of an oral calcium supplement. Monitor for decreased therapeutic effects of oral quinolones if administered with oral calcium supplements.

Dicumarol: The quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of dicumarol.

Warfarin: The quinolone antibiotic, nalidixic acid, may increase the anticoagulant effect of warfarin.