Probenecid Penicillins

PENICILLINS PROBENECID, SULFINPYRAZONE t penicillin levels Uncertain Watch for t incidence of side-effects... 

Penicillin Probenecid Sulfisoxazole Aspirin Sulfamethoxy pyridazine Warfarin Diflunisal Phenylbutazone ... 

Penicillin + probenecid Threefold increase in serum penicillin level with increase also in spinal fluid levels but decreased brain level Displacement from protein binding, decreased renal tubule secretion and decrease biliary excretion Combination can be used when high serum and spinal fluid levels are required... 

The co-administration of drugs which inhibit the transporters involved in renal tubular secretion can reduce the urinaty excretion of drugs which are substrates of the transporter, leading to elevated plasma concentrations of the drugs. For example, probenecid increases the plasma concentration and the duration of effect of penicillin by inhibiting its renal tubular secretion. It also elevates the plasma concentration of methotrexate by the same mechanism, provoking its toxic effects. 

In those with gout, the serum uric acid level is usually elevated. Sulfinpyrazone increases the excretion of uric acid by the kidneys, which lowers serum uric acid levels and consequently retards the deposit of urate crystals in the joints. Probenecid (Benemid) works in the same manner and may be given alone or with colchicine as combination therapy when there are frequent, recurrent attacks of gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins. 

Aqueous crystalline Penicillin G, 3-4 million units IV every 4 hours for 10-14 days or procaine Penicillin G, 2.4 million units IM q.d., plus 500iug of probenecid poq i.d. for 10 14 days... 

Procaine penicillin G 2.4 million units administered intramuscularly once daily, plus probenecid 500 mg orally four times daily for 10 to 14 days. 

Salicylates, sulfonamides, probenecid, and high dose penicillin may... 

Penicillins and cephalosporins Probenecid, aspirin Blocked excretion of /3-lactams Use if prolonged high concentration of /J-lactam desirable... 

Aqueous procaine penicillin G 2.4 million units IM daily plus probenecid 500 mg orally four times daily, both for 10-14 days 6 Aqueous crystalline penicillin G 50,000 units/kg IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days or... 

The absorption and excretion of carbenicillin in man has been reported [396]. The antibiotic is not absorbed intact from the gut intramuscular injection (which is painful) often provides adequate serum levels (approximately 20 Mg/ntl) but infections with Pseudomonas strains having minimum inhibitory concentrations up to, or higher than, 100 Mg/ml require intravenous thbrapy to achieve such levels. No evidence of active metabolite formation has been obtained. Marked reductions in the half-life (and serum levels) of carbenicillin follow extracorporeal dialysis or peritoneal dialysis, the former producing the most striking effect [397]. These results were, of course, obtained in patients with severe renal failure. Patients with normal renal function rapidly eliminate the drug but, as with all penicillins, renal tubular secretion can be retarded by concurrent administration of probenecid. 

Combination with probenecid. Renal elimination of penicillin occurs chiefly via the anion (acid)-secretory system of the proximal tubule (-COOH of 6-APA). The acid probenecid (p. 316) competes for this route and thus retards penicillin eUmination ... 

Penicillin or cephalosporin therapy The PSP excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about the normal rate when dosage of probenecid is adequate. 

Gonorrhea (uncomplicated) - Give probenecid as a single 1g dose immediately before or with 4.8 million units penicillin G procaine, aqueous, divided into at least 2 doses. 

Probenecid also inhibits the tubular secretion of most penicillins and cephalosporins and usually increases plasma levels by any route the antibiotic is given. Pharmacokinetics Probenecid is well absorbed after oral administration and produces peak plasma concentrations in 2 to 4 hours. It is highly protein bound (85% to 95%). Probenecid is excreted in the urine primarily as metabolites. 

Procaine penicillin G, 2.4 million units/day IM plus probenecid 500 mg orally 4 times/day, both for 10 to 14 days. Many recommend benzathine penicillin G, 2.4 million units IM once/wk for up to 3 wk following completion of this regimen. 

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... 

Drugs that may affect penicillins include allopurinol, aminoglycosides (parenteral), aspirin, beta blockers, chloramphenicol, erythromycin, ethacrynic acid, furosemide, indomethacin, phenylbutazone, probenecid, sulfonamides, tetracycline, and thiazide diuretics. Drugs that may be affected by penicillins include aminoglycosides (parenteral), anticoagulants, beta blockers, chloramphenicol, cyclosporine, oral contraceptives, erythromycin, heparin, and vecuronium. 

Action Monobactam, -1- cell wall S5mth Dose Adul. 1—2 g IV/EM q6-12h Peds. Premature 30 mg/kg/dose IV ql2h Term children 30 mg/kg/dose q6-8h X in renal impair Caution [B, +] Disp Inj SE NA /D, rash, pain at inj site Interac tions T Effects W/probenecid, aminoglycosides, i-lactam antibiotics X effects W7 cefoxitin, chloramphenicol, imipenem EMS Monitor for S/Sxs of super Infxn may cause aUCTgic Rxns rare cross-sensitivity Rxns to penicillins and cephalosporins have been rqwrted OD May cause Szs symptomatic and supportive... 

Uses Infxns of resp tract, skin/soft tissue, scarlet fevCT, S5 philis Action Bactericidal -1- cell wall synth Dose Adults. 0.6-4.8 million Units/d in doses ql2-24h give probenecid at least 30 min prior to PCN to prolong action Feds. 25,000-50,000 Units/kg/d IM daily-bid Caution [B, M] Contra AU gy Disp Inj SE Pain at inj site, int stitial n hritis, anaphylaxis Interactions t Effects W/probenecid t penicillin 1/2-life Wf ASA, furosemide, indomethacin, sulfonamides, thiazide diuretics T risk of bleeding W/ anticoagulants -1- effects Wf chloramphenicol, macrolides, tetracyclines -1- effects OF OCPs EMS See Penicillin G, Aqueous OD See Penicillin G, Aqueous... 

Probenecid can impair the renal active secretion of a variety of acidic compounds, including sulfinpyrazone, sulfonylureas, indomethacin, penicillin, sulfonamides, and 17-ketosteroids. If these agents are to be given concomitantly with probenecid, their dosage should be modified appropriately. Salicylates interfere with the clinical effects of both sulfinpyrazone and probenecid and should be avoided in patients treated with uricosuric agents. Uricosuric agents also can influence the volume of distribution and hepatic metabolism of a number of drugs. 

Penicillin G is excreted by the kidneys, with 90% of renal elimination occurring via tubular secretion and 10% by glomerular filtration. Probenecid blocks tubular secretion and has been used to increase the serum concentration and prolong the half-life of penicillin G and other penicillins. Additional pharmacokinetic information can be found in Table 45.1. 

Tubular secretion The active secretory systems can rapidly remove the protein-bound drugs from the blood and transport them into tubular fluid as the drugs that are bound to proteins are not readily available for excretion by filtration. The drugs known to be secreted by organic anion secretory system (i.e. strong acids) are salicylates, chlorothiazide, probenecid, penicillin etc. and cation (i.e. bases) includes catecholamines, choline, histamine, hexamethonium, morphine etc. 

The tubular secretion of penicillin is inhibited by probenecid, so that the blood concentration and its half life (therapeutic effects) is prolonged with the simultaneous use of these two drugs. Phenylbutazone can block the renal tubular reabsorption of uric acid, leading to uricosuria. 

Gonococcal infection Procaine penicillin along with probenecid can be used. 

Two main effects occur here. First, change in the pH of urine—weak bases, such as pethidine, are more easily excreted in an acid urine while alkalinisation promotes excretion of weak acids, such as salicylates and phenobarbital. Second, drugs that compete for an active excretion mechanism will reduce each other s elimination—probenecid was used in the early days of penicillin to conserve the drug, while less desirable interactions also occur, e.g. chlorpropamide and phenylbutazone interact to give increased levels of chlorpropamide and a danger of hypoglycaemia. 

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