Probenecid Nafcillin

Excretion - Penicillins are excreted largely unchanged in the urine by glomerular filtration and active tubular secretion. Nonrenal elimination includes hepatic inactivation and excretion in bile this is only a minor route for all penicillins except nafcillin and oxacillin. Excretion by renal tubular secretion can be delayed by coadministration of probenecid. Elimination half-life of most penicillins is short (no... 

Excretion The primary route of excretion is through the organic acid (tubular) secretory system of the kidney (see p. 224), as well as by glomerular filtration. Patients with impaired renal function must have dosage regimens adjusted. Thus the Xyz of penicillin G can increase from a normal of 1/2 -1 hour to 10 hours in individuals with renal failure. Probenecid inhibits the secretion of penicillins. Nafcillin is primarily eliminated through the biliary route. [Note This is also the preferential route for the acylureido penicillins in cases of renal failure.]... 

Ceftriaxone (A) Clindamycin (A) Clofibrate (A) Dexamethasone (N) Diazepam (B) Diazoxide (A) Dicloxacillin (N) Digitoxin (N) Etoposide (N) Ibuprofen (A) Indomethacin (A) Nafcillin (A) Naproxen (A) Oxacillin (A) Phenylbutazone (A) Phenytoin (A) Probenecid (A) Salicylic acid (A) Sulfisoxazole (A) Teniposide (N) Thiopental (A) Tolbutamide (A) Valproic acid (A) Warfarin (A)... 

Clinically important, potentially hazardous interactions with acitretin, aldesleukin, aminoglycosides, amiodarone, amoxicillin, ampicillin, aspirin, bacampicillin, bismuth, carbenicillin, chloroquine, cisplatin, cloxacillin, co-trimoxazole, dapsone, demeclocycline, dexamethasone, diclofenac, dicloxacillin, etodolac, etoricoxib, etretinate, fenoprofen, flurbiprofen, folic acid antagonists, haloperidol, hydrocortisone, ibuprofen, indomethacin, influenza vaccines, ketoprofen, ketorolac, lithium, magnesium trisalicylate, meclofenamate, mefenamic acid, methicillin, mezlocillin, minocycline, nabumetone, nafcillin, naproxen, NSAIDs, omeprazole, oxacillin, oxaprozin, oxytetracycline, paromomycin, penicillin G, penicillin V, penicillins, phenylbutazone, piperacillin, piroxicam, polypeptide antibiotics, prednisolone, prednisone, probenecid, procarbazine, rofecoxib, salicylates, salsalate, sapropterin, sulfadiazine, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfisoxazole, sulindac, tazobactum, tenoxicam, tetracycline, ticarcillin, tolmetin, trimethoprim, vaccines... 

Nafcillin and aminoglycosides are chemically inactivated and should not be mixed together. Probenecid blocks renal tubular secretion of penicillins however, this interaction has only a small effect on the excretion of nafcillin. 

B. Pharmacokinetics Penicillins vary in their resistance to gastric acid and therefote vary in their oral bioavailability. They are polar compounds and are not metabolized extensively. They are usually excreted unchanged in the urine via gloinemlar filtration and tubular secretion, the latter process being inhibited by probenecid. Ampicillin and nafcillin are excreted partly in the bile. The plasma half-lives of most penicillins vary from one-half to 1 hour. Procaine and benzathine forms of penicillin G are administered intramuscularly and have long plasma half-lives because the active drug is released very slowly into the bloodstream. Most penicillins cross the blood-brain barrier only when the meninges are inflamed. 

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... 

A study in 5 healthy subjects given 500 mg of intravenous nafcillin sodium with probenecid, 1 g given orally the previous night and 1 g given 2 hours prior to the antibacterial, showed that the urinary recovery of nafcillin was reduced from 30% to 17%, and its AUC was approximately doubled. ... 

In each case the penicillin competes with the probenecid for excretion by the kidney tubules, although with nafcillin, non-renal clearance may also play a part. 

Waller ES, Sharanevych MA, YakatanGJ. The effect of probenecid on nafcillin disposition. J Clin Pharmacol (1982) 22, 482-9. 

---