50 kg: 25 mg/kg body weight (or 700mg/m 2) PO once with PCN; for maintenance, increase to 40 mg/kg body weight (or 1.2 g/m 2) per day PO divided q6hr; not to exceed 500 mg/dose >50 kg: 500 mg PO four times daily Probenecid has been shown to decrease lorazepam clearance by about 50% and increase its elimination half-life. (ed.). Hence probenecid can be combined penicillins to increase their duration of action. ... increasing plasma concentrations and prolonging the terminal half-life of penicillin and other penicillin derivatives. Hepatic Dose : Metabolism is hepatic, use with caution in severe impairment. Probenecid and penicillin exhibits this type of interaction: a. enzyme induction c. alteration in gastric emptying ... increase half life d. un-ionized, not reabsorbed, increases elimination rate. Probenecid increased penicillin T/2 from an average of 40.4 to 104.3 minutes. Approximately 20% of renal excretion occurs by glomerular filtration and ~80% by active tubular secretion—a process that may be deliberately inhibited (to prolong effective concentrations in the body) by probenecid and other weak organic acids. Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine.It is primarily used in treating gout and hyperuricemia.. Probenecid was developed as an alternative to caronamide to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects. Probenecid was introduced in the 1950’s to reduce the renal elimination and extend the plasma half-life of penicillins. Probenecid. These medicines include acetaminophen, naproxen, indomethacin, ketoprofen, meclofenamate, lorazepam, rifampin, acyclovir, ganciclovir and zidovudine. Anuria may increase the half-life of penicillin G (normally ~30 min) to 10 hr. This effect is exploited therapeutically in the treatment of cellulitis and other infections. As excretion of penicillins somewhat decreased, the duration of action increases. Probenecid interferes with the renal secretion of penicillin, other beta-lactam antibiotics, and methotrexate, thereby decreasing their renal clearance, increasing their half-life, and elevating their plasma concentrations (if dosage adjustments are not made). Contraindicated >2 years old. Probenecid increases the mean plasma elimination half-life of a number of other medicines which can lead to increased peak plasma concentrations. In a group of elderly patients with normal serum creatinine, penicillin T/2 was prolonged due to age‐dependent decrease in renal function. The clinical significance of this effect on Prolong Penicillin Serum Levels 2 years old. Decreased urinary recycling, increases elimination rate constant hence a. increases half life Following oral administration of 2 g of probenecid, plasma half-life of the drug ranges from 4-17 hr; the half-life decreases as the dose decreases from 2 g to 500 mg. McEvoy, G.K. Ketorolac: Avoid contamittant use with ketorolac since its half-life is increased 2-fold. Probenecid: Increases plasma levels of penicillin and acyclovir. This drug interaction can be used for a clinical benefit. B. Probenecid increases the serum concentrations of cinoxacin [171], enoxacin [172], and nalidixic acid [173] probably by inhibiting their renal tubular secretion. In addition, pretreatment with probenecid shortened the induction time (85 vs. 109 seconds) of midazolam in presurgical patients. American Hospital Formulary Service - Drug Information 93. The effect of several drugs on the active renal tubular transport mechanism of penicillin was studied. Probenecid is such a drug that inhibits active tubular secretion thereby inhibits secretion of penicillins into renal tubules. This bulletin will focus on the use of probenecid to extend the plasma half-life of beta-lactam antibiotics.