Influence of Probenecid and Food on the Bioavailability of Cephradine in Normal Male Subjects

Mischler, Terrence W.; Sugerman, A. Arthur; Willard, David A.; Brannick, L. J.; Neiss, E. S.

doi:10.1002/j.1552-4604.1974.tb01380.x

Cited by 42 publications

(16 citation statements)

References 4 publications

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“…Probenecid Ig as either a single dose given together with cefradine or administered Ih before, or 2 doses at 7 and Ih before the antibiotic resulted in elevated serum cefradine concentrations and reduced CL for all regimens versus cef- Abbreviations: Vd = volume of distribution; NA = not available; NS = not statistically significant, as originally reported; PO = oral; IV = intravenous; 1M = intramuscular; qxh = every x hours; tid = 3 times daily. radine alone (Mischler et al 1974). Only the 2-dose probenecid pretreatment regimen resulted in significant serum antibiotic concentrations beyond 8h following cefradine administration, a time when serum concentrations are negligible with cefradine alone.…”

Section: Cefradinementioning

confidence: 94%

Cephalosporin-Probenecid Drug Interactions

Brown

1993

Clinical Pharmacokinetics

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The effect of concurrent probenecid administration on the pharmacokinetics of cephalosporin antibiotics varies with the available cephalosporins. Most cephalosporins are affected to some degree by concurrent probenecid administration, although ceforanide, ceftazidime, ceftriaxone and latamoxef (moxalactam) have no significant changes in pharmacokinetics. For those cephalosporins affected by probenecid, the predominant findings are impairment in renal clearance resulting in increased peak serum concentrations, an increased area under the concentration-time curve (AUC), and both delayed and prolonged recovery of the cephalosporin in the urine. The distribution of the cephalosporins is affected to varying degrees, with reports of increased penetration into ocular, central nervous system and blister fluids noted with some agents. The clinical relevance of the changes in cephalosporin distribution associated with probenecid administration has not been investigated. The dose and timing of probenecid administration appear to be major determinants in any possible interaction. Studies with ceftizoxime and cefoxitin suggest that larger probenecid doses result in greater changes in the pharmacokinetics of cephalosporins. Prolonged probenecid therapy before administration of a cephalosporin did not seem to be as relevant as the probenecid dosage in determining the magnitude of the interaction. Probenecid administration with or immediately before cephalosporin administration appears able to produce these documented changes in cephalosporin pharmacokinetics. The route of administration (oral versus parenteral) of either prolosporin pharmacokinetics. The route of administration (oral versus parenteral) of either probenecid or the cephalosporin does not appear to influence the characteristics of the interactions. The therapeutic efficacy of a combination of a cephalosporin with probenecid has been most thoroughly studied for single-dose treatment of gonorrhoea. The addition of probenecid to cephalosporin therapy results in sustained systemic concentrations adequate for eradication of Neisseria gonorrhoeae. Regimens involving either second or third generation cephalosporins demonstrate good success rates with single-dose therapy. However, the success of ceftriaxone administered alone for treatment of both penicillase-producing and non-penicillase-producing strains of N. gonorrhoeae suggests that the addition of probenecid is unnecessary. The use of probenecid, in combination with cephalosporins, to enhance the treatment of other venereal and systemic infections has preliminary, inconclusive support.

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Section: Cefradinementioning

confidence: 94%

Cephalosporin-Probenecid Drug Interactions

Brown

1993

Clinical Pharmacokinetics

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“…Because of its unique physiological location, a decrease in renal secretion due to competitive inhibition of proximal tubular secretion may produce an increase in systemic drug exposure, thereby resulting in clinically signifi cant changes in overall drug PK. For example, renal tubular secretion is inhibited by the co-administration of OAT inhibitor probenecid, leading to increased systemic exposure of penicillin and cephalosporin antibiotics (Mischler et al, 1974;Sircar et al, 2002). On the other hand, OAT1 and OAT3 are expressed on the basolateral membrane of proximal tubular cells and thus exist at the physiological interface of drug-related nephrotoxicity (Izzedine et al, 2005).…”

Section: Transporter Effects On Renal Secretionmentioning

confidence: 99%

Drug transporters in drug discovery and development

Cheng¹,

Lai²

2013

Transporters in Drug Discovery and Development

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“…The peak concentration of cephalexin in serum (23. 4 ,tg/ml) was lowered by 62%, whereas that for cephradine (21.3 ytg/ml) was lowered by 54%, by coadministration of antibiotic and milk (Fig. 1).…”

Section: Discussionmentioning

confidence: 91%

“…The agent has minimal toxicity in humans and is not appreciably bound to plasma proteins. Studies performed in adults and in a limited number of older children indicate that cephradine is rapidly absorbed after oral administration to fasting patients, and bioavailability is not appreciably affected by the concurrent administration of food (4,7). Serum concentrations, half-life times, and urinary levels are comparable to those of cephalexin when both drugs are administered in equivalent dosages.…”

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confidence: 98%

Pharmacokinetics of Cephradine Suspension in Infants and Children

Ginsburg

McCracken

1979

Antimicrob Agents Chemother

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The pharmacokinetics of cephradine suspension were studied in 16 infants and children who were 13 months to 8 years and 3 months of age (means age, 3.5 years). Mean peak concentrations of 21.3 and 9.9 ,tg/ml were achieved at 30 min after administration of 60-mg/kg doses to fasting and nonfasting patients. The area under the serum concentration-time curve was 26% larger in fasting than in fed subjects. The half-life of cephradine in serum was 0.8 and 1.0 h in fasting and fed groups, respectively. Antimicrobial activity was detected in 49% of all salivary samples; in 75% of specimens, the concentrations were less than the 50% minimum inhibitory concentration for most pneumococci and group A streptococci. Urinary concentrations of cephradine ranged from 28 to 8,760 ,ug/ml and were independent of feeding status.Cephradine is a new semisynthetic cephalosporin that has a chemical structure and spectrum of antimicrobial activity similar to those of cephalexin (1). The agent has minimal toxicity in humans and is not appreciably bound to plasma proteins. Studies performed in adults and in a limited number of older children indicate that cephradine is rapidly absorbed after oral administration to fasting patients, and bioavailability is not appreciably affected by the concurrent administration of food (4, 7). Serum concentrations, half-life times, and urinary levels are comparable to those of cephalexin when both drugs are administered in equivalent dosages.Because of the limited amount of pharmacokinetic data for cephradine in infants and young children, the following investigation was undertaken. MATERIALS AND METHODSThe study was conducted in the Out-Patient Clinic of Children's Medical Center, Dallas, Texas. Infants and children with impetigo were eligible for study.The decision to initiate antimicrobial therapy was made independent of the investigators. Prior to enrollment in the study written parental consent was obtained for each study patient. Sixteen infants and children aged from 13 months to 8 years and 3 months (mean, 3.5 years) were studied. Nine were male and seven were female. Their weights ranged from 7.2 to 28.2 kg (mean, 15.8 kg), and their heights ranged rom 62 to 124 cm (mean, 94.8 cm). The average body surface area was 0.91 m.2 Cephradine was administered as an oral suspension (125 or 250 mg per 5 ml) in a daily dosage of 60 mg/kg in four divided doses. Most children were studied twice, once while fasting and once when the antibiotic was given with 4 ounces (ca. 120 ml) of milk. The order of administration of the drug was determined by a random code. There was a 5-to 7-day interval between studies in most children. All studies were initiated between 8 and 9 a.m. after a 10-to 12-h fast. None of the children was receiving any other medication prior to or at the time of the studies. A research nurse administered the drug to all study patients. Blood samples were obtained immediately before and at 0.5, 1, 2, 4, and 6 h after the dose. Saliva was collected in capillary pipettes at 2, 4, and 6 h after the ...

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Influence of Probenecid and Food on the Bioavailability of Cephradine in Normal Male Subjects

Cited by 42 publications

References 4 publications

Cephalosporin-Probenecid Drug Interactions

Cephalosporin-Probenecid Drug Interactions

Drug transporters in drug discovery and development

Pharmacokinetics of Cephradine Suspension in Infants and Children

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