Probenecid: an unexplained effect on cephalosporin pharmacology.

Welling, P. G.; Dean, Scott N.; Selen, Arzu; Kendall, M. J.; Wise, R.

doi:10.1111/j.1365-2125.1979.tb01032.x

Cited by 45 publications

(24 citation statements)

References 14 publications

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“…The concept has not been considered for steady state or infusion conditions. Very recently it was noted that probenecid raised the serum levels of orally administered cephradine and cefaclor, in addition to retarding their excretion (Welling, Dean, Selen, Kendall & Wise, 1979).…”

Section: Discussionmentioning

confidence: 99%

The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers.

Reeves¹,

Bullock²,

Bywater³

et al. 1981

Brit J Clinical Pharma

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1 Cefoxitin was given by acute intravenous injection to six healthy volunteers, in a crossover study to investigate the effects of concurrent probenecid administration. 2 Serum antibiotic concentrations were determined by microbiological assay. Cefoxitin concentrations were simultaneously determined in the fluid of blisters produced by topical cantharides. All antibiotic was accounted for in the urine. 3 Cefoxitin was administered by intravenous infusion, subsequent to a loading dose, to produce steady state levels in the region of 10 microgram/ml, in one volunteer. The procedure was later repeated after prior administration of probenecid in the same subject. 4 Pharmacokinetic analyses indicated significant changes only in the parameters associated with renal excretion of drugs. Clearance was reduced by half. 5 The absolute and relative amounts of antibiotic in the central and peripheral compartments were calculated for both modes of administration. In the acute study probenecid produced a small change in distribution away from the peripheral or tissue compartment, towards the central compartment. 6 There was no elevation of initial serum concentrations and sustained levels of antibiotic could be accounted for principally by retarded excretion produced by probenecid, with little contribution by alteration in the disposition of antibiotic. 7 The sustained serum levels of cefoxitin that resulted from its decreased excretion were also reflected in blister fluid. It was concluded that the sustained cefoxitin levels produced by probenecid resulted in similar raised levels in the peripheral or “tissue” compartment, since the redistribution away from the peripheral compartment did not contribute materially to other changes in disposition of drug.

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Section: Discussionmentioning

confidence: 99%

The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers.

Reeves¹,

Bullock²,

Bywater³

et al. 1981

Brit J Clinical Pharma

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“…After the protocol was approved by the Thomas Jefferson University Committee on Research, 12 male volunteers, age 21 to 35 years, gave written informed consent to participate in the study. They 1 were all within ±10% of ideal body weight and judged 1 to be healthy on the basis of a normal physical exam-ination and the results of laboratory screening studies, including serum urea nitrogen and creatinine, and urinalysis.…”

Section: ) Materials and Methodsmentioning

confidence: 99%

Effect of orally administered probenecid on the pharmacokinetics of cefoxitin

Vlasses¹,

Holbrook²,

Schrogie³

et al. 1980

Antimicrob Agents Chemother

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To characterize the effects of orally administered probenecid on the phannacokinetics of cefoxitin in healthy male volunteers, we administered to one group of six subjects 2 g of cefoxitin by intravenous (i.v.) bolus either alone, with 1 g of probenecid concomitantly, or when 1 g of probenecid was administered 1 h previously by using a crossover design. Likewise, we administered to a second group of six subjects 2 g of cefoxitin intramuscularly (i.m.) Probenecid competitively inhibits the rena tubular secretion of other organic acids (20) anc has been used with penicillins and cephalospo rins to increase and sustain antibacterial concen trations to enhance therapeutic efficacy (3,8,11) Cefoxitin, a cephamycin derivative, is eliminatec primarily by glomerular filtration and tubulsi secretion (17). The purpose of the present stud) was to characterize the effect of probenecid or the blood and urine concentrations of intrave nously (i.v.) and intramuscularly (i.m.) admin istered cefoxitin. The portion of the study or i.v.-administered cefoxitin allowed a completE pharmacokinetic analysis ofthe effect of proben ecid on the disposition of cefoxitin. The portior on i.m.-administered cefoxitin allowed us to as sess the interaction under the conditions of comr mon clinical use (1).

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“…However, it is uncertain whether this is the only mechanism responsible for the increased plasma levels of drug in the presence of probenecid (Gibaldi & Schwartz 1968). Welling, Dean, Selen, Kendall & Wise (1979) examined the pharmacokinetics of two orally dosed cephalosporins, cephradine and cefaclor in the absence and presence of probenecid. The study appeared to show that the increase in serum levels of both antibotics in the presence of probenecid could not be fully explained by the decrease in their apparent elimination rates and might therefore involve a change in the distribution volume of the drug.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of cephradine given intravenously with and without probenecid.

Roberts¹,

Kendall²,

DeRuiter³

et al. 1981

Brit J Clinical Pharma

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1979) the influence of probenecid on the pharmacokinetics of intravenously administered cephradine has been investigated. 2 Intravenous administration of cephradine resulted in a bi-exponential curve and the level of antibiotic after 15 min was significantly greater when subjects received probenecid than when they did not. The influence of probenecid on urinary excretion of cephradine was similar to that observed previously.3 The increase in serum of cephradine due to probenecid could be accounted for by the decrease in the elimination rate of the antibiotic. These results are discussed in the light of other observations.

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Probenecid: an unexplained effect on cephalosporin pharmacology.

Cited by 45 publications

References 14 publications

The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers.

The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers.

Effect of orally administered probenecid on the pharmacokinetics of cefoxitin

Pharmacokinetics of cephradine given intravenously with and without probenecid.

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