Pharmacokinetics and safety of ceftriaxone in the neonate

Mulhall, Anne; Louvois, J de; James, Jemila

doi:10.1007/bf00441782

Cited by 24 publications

(16 citation statements)

References 16 publications

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“…Although SCE was administered in a lower dosage, both drugs offered VOL. 37,1993 on March 25, 2019 by guest http://aac.asm.org/ Downloaded from approximately equal antibacterial efficacy against the tested gram-negative bacteria. The increased SBA titer of SCE-2787 against S. aureus demonstrated the broader antibacterial spectrum of this new cephalosporin, which could be of clinical importance in the treatment of serious nosocomial infections.…”

Section: Discussionmentioning

confidence: 96%

“…Most of the reported side effects showed no correlation with physical or laboratory findings or high concentrations of both drugs in urine or blood. The adverse effects referring to the central nervous system were atypical for this class of substances (13,15,37,39). Only local and peripheral reactions (flush at the puncture site and itching eyes and nose) were probably drug related, because they were recorded during or directly after the 20-min infusion, and they are well-known adverse effects of cephalosporins (1,4,14,38).…”

Section: Discussionmentioning

confidence: 98%

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Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime

Paulfeuerborn

Müller

Börner

et al. 1993

Antimicrob Agents Chemother

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Ceftazidime and the new SCE-2787 are parenteral cephalosporins with a broad antimicrobial spectrum. Pharmacokinetics, serum bactericidal activities, and side effects were investigated in a randomized crossover study. A total of 12 healthy volunteers received a 20-min infusion of 1.5 g of SCE-2787 or 2.0 g of ceftazidime. Serum and urine concentrations were determined by the bioassay method and by high-pressure liquid chromatography (HPLC) Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. One hour after administration, we measured mean reciprocal bactericidal titers of SCE-2787 and ceftazidime, respectively, against Escherichia coli of 388 and 243, against KiebsieUla pneumoniae of 395 and 138, against Pseudomonas aeruginosa of 13.0 and 12.7, and against Staphylococcus aureus of 32.2 and 4.0. No severe side effects were observed in this single drug administration.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime

Paulfeuerborn

Müller

Börner

et al. 1993

Antimicrob Agents Chemother

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“…The stochastic simulations were then performed to identify a MIC value and dose range, which can be employed to evaluate E-R relationship of FDC in-vitro. The pop-PK parameters of all four groups were obtained from literature 18,19 and employed in carrying out stochastic simulations (For pop-PK parameters, refer to "stochastic simulations" subsection of "Materials and methods" section). The simulations were performed for OD and BD dose range of 30-120 mg/kg at MICs of 1,4,8,16,32, and 64 µg/mL for all four age groups (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…17 . In case of neonates, ceftriaxone's clearance and half life of 0.12 L/h and 15.4 hr, respectively were used; whereas sulbactam has 0.4 L/h and 9.24 hr of clearance and half life, respectively 18,19 . The concentration-profiles of once-a-day and twice-a-day dosing regimens were generated using CL and k e of each simulated subjects and %T>MIC comb was calculated for all simulated subjects for different exposures at all MIC values.…”

Section: Hollow Fiber Systemmentioning

confidence: 99%

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2016

IJPSR

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Increase in complexity and cost associated with pediatric safety and efficacy studies have reduced the interest of pharmaceutical companies to study biotherapeutics in pediatric population. Dose recommendations are being made as per patient body weight or body surface area, with the assumption of linearity in body size dose adjustments. In the present study, newer approach i.e. flat fixed age-based dosing is explored. Stochastic simulations were performed on once-a-day (OD) and twice-a-day (BD) dosage regimens of a fixed dose combination (FDC) of ceftriaxone/sulbactam (2/1) to identify a promising dose range that can effectively evaluate exposure-response (E-R) relationships of the FDC against bacterial infection in pediatric population. Selected dose range of 60-120 mg/kg of FDC was evaluated against ESBL infection using in-vitro systems (dilution method and hollow fiber method). Effect of dose, dose frequency, severity of infection and age groups were analyzed in age-based subgroups i.e. neonates, infant, child and toddler. Recommended dose for infants, child and toddler were 75-120 mg/kg based on severity of infection. However, physiologically-induced reduction in drug's clearance in neonates had resulted in lower dose recommendation against bacterial infection. Neonate dose of 120 mg/kg OD was best among all the exposures tested and its potential dose-related toxicity can be reduced either by reducing the doses (in mild infection) or by fractionating the dose into BD regimen (in severe infection). The E-R relationships of 120 mg/kg OD and BD dosage regimens in neonates were confirmed using in-vitro hollow fiber system.

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“…However, these dosage recommendations are based upon few pharmacokinetic data. Previous studies also did not stratify preterm infants according to gestational age (GA) or postnatal age, which has resulted in a substantial variability in pharmacokinetic parameters (3,(11)(12)(13)17). We have previously demonstrated that the pharmacokinetic behavior of ceftazidime in preterm infants is strongly dependent on GA and postnatal age.…”

mentioning

confidence: 99%

Once-daily versus twice-daily administration of ceftazidime in the preterm infant

Anker

Schoemaker

Heijden

et al. 1995

Antimicrob Agents Chemother

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Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to 31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia were randomized on day 1 of life in two groups. One group (n ‫؍‬ 13) was administered 25 mg of ceftazidime per kg of body weight once daily, and the other (n ‫؍‬ 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an intravenous bolus injection. An additional blood sample was taken at 24 h from the group dosed once a day. High-performance liquid chromatography was used to determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime were best described by using a one-compartment model. The half-life for the elimination of the drug from serum, apparent volume of distribution, total body clearance of ceftazidime, and inulin clearance were not significantly different for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups. However, trough concentrations in serum for the twice-daily group were significantly (P < 0.001) higher (42.0 ؎ 13.4 mg/liter) than those for the once-daily group (13.1 ؎ 4.7 mg/liter). The latter concentrations were all still substantially higher than the MIC of ceftazidime for major neonatal pathogens. We conclude that the currently recommended dosage of 25 mg of ceftazidime per kg twice daily for preterm infants with gestational ages below 32 weeks may be adjusted during the first days of life to one daily dose at 25 mg/kg, provided that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also given twice daily.Ceftazidime, an expanded-spectrum cephalosporin, is commonly used in the treatment of bacterial infections in the newborn (5). The currently recommended dosage regimen of ceftazidime for preterm infants less than 4 weeks old and whose birth weights are below 1,200 g is 25 to 100 mg/kg of body weight given intravenously twice daily (18). However, these dosage recommendations are based upon few pharmacokinetic data. Previous studies also did not stratify preterm infants according to gestational age (GA) or postnatal age, which has resulted in a substantial variability in pharmacokinetic parameters (3,(11)(12)(13)17). We have previously demonstrated that the pharmacokinetic behavior of ceftazidime in preterm infants is strongly dependent on GA and postnatal age. At a dosage of 25 mg of ceftazidime per kg given intravenously twice daily, high trough levels were observed, especially in infants with GAs below 32 weeks (21). High concentrations of beta-lactam antibiotics in serum and tissues do not result in a more rapid killing of bacteria (4), but they may lead to neutropenia and the impairment of cellular and humoral immune responses (14). We therefore designed a prospective randomized study to evaluate the pharmacokinetic effects of reducing the dosage of ceftazidime from 25 mg/kg twice daily to 25 m...

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Pharmacokinetics and safety of ceftriaxone in the neonate

Cited by 24 publications

References 16 publications

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime

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Once-daily versus twice-daily administration of ceftazidime in the preterm infant

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