Effect of Probenecid on the Apparent Volume of Distribution and Elimination of Cloxacillin

Nauta, Ernst H.; Mattie, H.; Goslings, W. R. O.

doi:10.1128/aac.6.3.300

Cited by 18 publications

(7 citation statements)

References 6 publications

(3 reference statements)

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“…On the other hand probenecid was shown to have no affect on the distribution characteristics of cloxacillin in humans (Nauta, Mattie & Goslings, 1974), did not change the relative concentrations of ampicillin and oxacillin in fibrin clots and serum of rabbits (Barza, Brusch, Bergeron & Weinstein, 1974), and had no effect on antibacterial action of cephradine in experimentally infected mice (Kunste & Mattie, 1978).…”

Section: Discussionmentioning

confidence: 98%

Probenecid: an unexplained effect on cephalosporin pharmacology.

Welling¹,

Dean²,

Selen³

et al. 1979

Brit J Clinical Pharma

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1 The influence of probenecid on serum levels and urinary excretion of orally administered cephradine and cefaclor has been investigated. 2 Probenecid caused serum levels of both antibiotics to be increased and also prolonged. Urinary excretion of antibiotic activity was slightly but not significantly decreased by probenecid during the initial 6 h postdosing. It was significantly increased in 6‐12 h urine, but only a small percentage of the doses were excreted during that period. 3 The increased serum levels of antibiotic were greater than could be accounted for by reduced elimination rate alone. Possible mechanisms to account for increased circulating levels of antibiotic in the presence of probenecid are discussed in the light of previous observations on probenecid induced changes in tissue distribution of beta‐lactam antibiotics.

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Section: Discussionmentioning

confidence: 98%

Probenecid: an unexplained effect on cephalosporin pharmacology.

Welling¹,

Dean²,

Selen³

et al. 1979

Brit J Clinical Pharma

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“…However, the degree of active tubular transport undergone by individual ,8-lactams is highly variable (Bins & Mattie 1988). Tubular transport is blocked by probenecid (Overbosch et al 1987), as is hepatic transport (Nauta et al 1974).…”

Section: Eliminationmentioning

confidence: 99%

Clinical Pharmacokinetics of Aztreonam

Mattie

1988

Clinical Pharmacokinetics

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Aztreonam (azthreonam) is practically completely absorbed after intramuscular injection. After intravenous injection plasma concentrations follow a 2-compartment open model, with a t1/2 alpha of 0.20 hours. Volume of distribution at steady-state (Vdss) after intravenous or intramuscular injection is about 0.16 L/kg (0.42 L/kg for the free drug). After oral administration less than 1% of the drug is absorbed. Over a large dosage range plasma concentrations increase linearly with dose. No accumulation occurs after multiple dosing. Plasma binding in healthy subjects is about 56% and is not concentration dependent. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma concentration seems to depend mainly on the composition of the tissue. In inflamed meninges, penetration of aztreonam into CSF is more rapid than with uninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breast milk. The main route of elimination of aztreonam is by the kidney, partly by active tubular excretion, but this can be inhibited by probenecid. Extrarenal clearance is probably due to excretion by the liver. Metabolism occurs to a very limited extent. Total plasma clearance in healthy adults is about 140 ml/min (8.4 L/h) or 2 ml/min/kg (0.12 L/h/kg), and terminal half-life is 1.7 hours. In children clearance is similar to that in adults when expressed as a function of bodyweight, but in neonates, especially in low birthweight infants, it is less [about 1 ml/min/kg (0.06 L/h/kg)]. In various disease states the Vdss of aztreonam is not appreciably different from that found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Probenecid has been reported to decrease the ClI, of cloxacillin, cinoxacin, and cefazedone (13,15,18) due to competition for a common metabolic pathway or an inhibition of biliary clearance. This effect of probenecid would be most evident with drugs that are extensively metabolized.…”

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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Effect of Probenecid on the Apparent Volume of Distribution and Elimination of Cloxacillin

Cited by 18 publications

References 6 publications

Probenecid: an unexplained effect on cephalosporin pharmacology.

Probenecid: an unexplained effect on cephalosporin pharmacology.

Clinical Pharmacokinetics of Aztreonam

Effect of orally administered probenecid on the pharmacokinetics of cefoxitin

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