Cephalosporin tubular reabsorption

Cephaloridine contains a quaternary nitrogen, exists as a zwitterion under physiological conditions and has structural similarities with carnitine. Proximal tubule cells are the internal sites of carnitine acylation [137]. Cephalosporin and carbapenem antibiotics inhibit carnitine tubular reabsorption [68, 138] and mitochondrial uptake of acylcarnitine leading to massive acylcarnitinuria [67]. Newer p-lactam such as cefepime and cefoselis, which possess a quaternary nitrogen as does carnitine, may also inhibit carnitine tubular reabsorption [88]. 

Inhibit proximal tubular reabsorption of urate, but ineffective if GFR < 50 mL/min. Also inhibit secretion of many acidic drugs, eg, cephalosporins, fluoroquinolones. 

A) Oral bioavailability is affected by first-pass hepatic metabolism Only third-generation cephalosporins cross the blood-brain barrier Procaine penicillin G is the most commonly used intravenous form of the antibiotic Renal tubular reabsorption of beta-lactams is inhibited by probenecid Nafcillin and ceftriaxone are eliminated mainly via biliary secretion The mechanism of antibacterial action of cephalosporins involves (A) Inhibition of the synthesis of precursors of peptidoglycans Interference with the synthesis of ergosterol Inhibition of transpeptidation reactions Inhibition of beta-lactamases Binding to cytoplasmic receptor proteins... 

Probenecid inhibits renal tubular reabsorption of water and by this meehanism enhanees the urinary excretion of uric acid. This lowers the level of urate in the serum. It thus serves as a potent uricosuric agent in the treatment of gout. Probenecid also blocks the renal tubular seeretion of penicillins and cephalosporins. It is, therefore, used as an adjuvant therapy with penicillin V or G, ampicillin, cloxacillin, oxacillin, methicillin and naficillin to increase and prolong their plasma levels. Besides it also enhances the plasma levels of anti-inflammatory agents like naproxen and indomethacin, and a host of medicinal compounds such as sulphonamides, sulphonylureas, dapsone, etc. 

Mechanism of Action An antigout agent that competitively inhibits reabsorption of uric acid at the proximal convoluted tubule. Also, inhibits renal tubular secretion of weak organic acids, such as penicillins. Therapeutic Effect Promotes uric acid excretion, reduces serum uric acid level, and increases plasma levels of penicillins and cephalosporins. 

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