Probenecid Ciprofloxacin

Ciprofloxacin (Cipro, Cipro XR, Proquin XR) [Antibiotic/ Fluoroquinolone] Uses Rx lower resp tract, sinuses, skin skin structure, bone/joints, urinary tract Infxns including prostatitis Action Quinolone antibiotic DNA gyrase Dose Adults. 250-750 mg PO ql2h XR 500-1000 mg PO q24h or 200-400 mg IV ql2h in renal impair Caution [C, /-] Children <18 y Contra Component sensitivity Disp Tabs, susp, inj SE Restlessness, N/V/D, rash, ruptured tendons, T LFTs Interactions T Effects Wf probenecid T effects OF diazepam, theophylline, caffeine, metoprolol, propranolol, phenytoin, warfarin effects W/ antacids, didanosine, Fe salts. Mg, sucralfate, Na bicarbonate,... 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

Renal clearance accounts for 61% of the total body clearance of ciprofloxacin in humans (350). Coadministration of probenecid reduces the total body and renal clearance to 59% and 36% of the control value, respectively, but has no effect on the nonrenal clearance (336). The transporters involved in the renal elimination of ciprofloxacin remains unknown. 

Jaehde U, Sorgel F, Reiter A, et al. Effect of probenecid on the distribution and elimination of ciprofloxacin in humans. Clin Phamacol Ther 1995 58 532-541. 

PROBENECID QUINOLONES -CIPROFLOXACIN, LEVOFLOXACIN, NALIDIXIC ACID, NORFLOXACIN t ciprofloxacin, nalidixic acid and norfloxacin levels Uncertain Watch for t incidence of side-effects. Moxifloxacin, ofloxacin and sparfloxacin do not seem to interact and could be used as alternative therapy... 

Uncomplicated anogenital infections amoxicillin with probenecid by mouth spectinomycin i.v., cefotaxime i.m. or ciprofloxacin by mouth may be used for penicillin-allergic patients. 

The renal excretion of ciprofloxacin was reduced and plasma concentrations increased by probenecid (79). 

Ceftriaxone 250 mg IM once or ciprofloxacin 500 mg p.o. once or norfloxacin 800 mg p.o. or cefuroxime axetil 1 g p.o. once plus probenecid 1 g or cefotaxime 1 g IM once or ceftizoxime 500 mg IM once plus Doxycycline 100 mg two times daily for 7 days or tetracycline 500 mg four times daily for 7 days... 

Probenecid increases the serum ieveis and/or decreases the urinary excretion of cinoxacin, ciprofloxacin, clinafloxacin, enoxacin, fleroxacin, levofloxacin, nalidixic acid and norfloxacin. The ciinicai importance of these changes is uncertain, but is seems iikeiy they wiii oniy be important in the presence of other drugs that aiso affect renai excretion. Grepafloxacin, moxifloxacin, sparfloxacin, and probably ofloxacin, appear not to interact with probenecid. 

In one study, probenecid 1 g, given 30 minutes before ciprofloxacin 500 mg, was found to reduce the renal clearance of ciprofloxacin by up to 50%. Other pharmacokinetic parameters (maximum serum levels, AUC) were unchanged and no accumulation of ciprofloxacin appeared to occur, probably due to an increase in extra-renal elimination. ... 

Another study found that the renal clearance of ciprofloxacin was reduced by 64% by probenecid. However, in contrast to the other study cited, the AUC of ciprofloxacin was increased by 74% and the AUC of its 2-aminoethylamino metabolite was increased by 234%. As a consequence, levels of ciprofloxacin in tears, sweat and saliva were also increased, but probenecid had no direct effect on ciprofloxacin distribution into these fluids. ... 

Landersdorfer CB, Kirkpatrick CM, Kinzig M, Bulitta JB, Holzgrabe U, Jaehde U, Reiter A, Naber KG, Rodamer M, Sorgel F. Competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by probenecid. Br J Clin Pharmacol 2010 69(2) 167-78. 

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