Ceftriaxone pharmacokinetics in newborn infants

McCracken, George H.; Siegel, Jane D.; Threlkeld, Norma; Thomas, Marion L.

doi:10.1128/aac.23.2.341

Cited by 41 publications

(19 citation statements)

References 5 publications

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“…The apparent volume o f dis tribution was consistent with values previ ously reported for a similar age group [1,[7][8][9]. The mean elim ination half-life of 3.7 h was close to the values of 4.0 h [4] and 4.1 h [1] but was shorter than 5.4 h [8] in in fants and children and 5.2-8.4h in neo nates [5].…”

Section: Pharmacokineticssupporting

confidence: 75%

“…As expected, the steady-state peak and trough serum concentrations of ceftriax one were higher than those observed after the first dose [1,4,5,[7][8][9]. The pharm aco kinetics were more variable after the load ing dose com pared to the maintenance dose at steady-state.…”

Section: Pharmacokineticsmentioning

confidence: 52%

“…An im portant pharm acokinetic character istic o f cefriaxone is its long elim ination half-life, allowing twice daily adm inistra tion in infants and children [1,2,5,[7][8][9]. These studies, however, have reported the pharm acokinetics [1,4,[6][7][8] and cerebro spinal fluid concentrations (CSF) [1,2,7] only after single doses of ceftriaxone.…”

Section: Introductionmentioning

confidence: 96%

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Ceftriaxone Kinetics and Cerebrospinal Fluid Penetration in Infants and Children with Meningitis

Nahata

Durrell

Barson³

1986

Chemotherapy

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20 patients (0.4–5.6 years old) receiving ceftriaxone for the treatment of bacterial meningitis were studied. Simultaneous serum and cerebrospinal fluid concentrations of ceftriaxone were determined by HPLC in 15 patients at 11.4–12.8 h after an intravenous loading dose of 75 mg/kg. Serum and cerebrospinal fluid concentrations ranged from 20.5 to 44.9 (31.3 ± 7.8) and from 1.1 to 8.0 (3.7+1.8) μg/ml, respectively. Cerebrospinal fluid concentrations ranged from 3 to 25% (12 ± 6%) of the simultaneous serum concentrations. In 6 patients, serum and cerebrospinal fluid concentrations were determined after maintenance doses of 50 mg/kg/l2 h. Serum and cerebrospinal fluid concentrations ranged from 120 to 144 and 2.3–4.9 μg/ml at 1.8–5.5 h after the first maintenance dose in 2 patients; 74–139 and 5.7–7.9 μg/ml at 1.3–5.8 h after the second dose in 3 patients and was 101 and 4.1 μg/ml at 4 h after the 3rd dose in 1 patient. Multiple blood samples were collected after the loading dose in 5 patients and after 9–10 days of maintenance doses in 3 patients. Steady-state peak and trough serum concentrations ranged from 295 to 440 and 32.6–44.8 μg/ml, respectively. After the loading and maintenance dose at steady-state, total body clearance averaged 1.17 and 0.64ml/min (p = 0.01); apparent volume of distribution averaged 0.37 and 0.261/kg (p > 0.05); and elimination half-life averaged 3.7 and 4.6 h (p = 0.01), respectively. These results suggest that (1) adequate cerebrospinal fluid concentrations of ceftriaxone can be achieved in patients with meningitis with the dosage regimen studied; (2) ceftriaxone kinetics may vary among infants and children with meningitis, and (3) the higher clearance of ceftriaxone noted at the higher dose may be partly due to its concentration-dependent plasma protein binding.

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Section: Pharmacokineticssupporting

confidence: 75%

Section: Pharmacokineticsmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Ceftriaxone Kinetics and Cerebrospinal Fluid Penetration in Infants and Children with Meningitis

Nahata

Durrell

Barson³

1986

Chemotherapy

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“…Free calcium concentrations were used for the calculations (27). The maximal expected CRO concentrations were obtained from values in the literature (17,24,26). Calculation of the saturation index was based on the product of the maximal expected serum CRO concentration obtained at steady state (post-distributive phase) and maximal free calcium concentration (the supraphysiologic concentration plus the bolus dose concentration) divided by the solubility product constant (27).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Potential Clinical Interaction between Ceftriaxone and Calcium

Steadman

Raisch

Bennett

et al. 2010

Antimicrob Agents Chemother

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In April 2009, the FDA retracted a warning asserting that ceftriaxone and intravenous calcium products should not be coadministered to any patient to prevent precipitation events leading to end-organ damage. Following that announcement, we sought to evaluate if the retraction was justified. A search of the FDA Adverse Event Reporting System was conducted to identify any ceftriaxone-calcium interactions that resulted in serious adverse drug events. Ceftazidime-calcium was used as a comparator agent. One hundred four events with ceftriaxone-calcium and 99 events with ceftazidime-calcium were identified. Adverse drug events were recorded according to the listed description of drug involvement (primary or secondary suspect) and were interpreted as probable, possible, unlikely, or unrelated. For ceftriaxone-calcium-related adverse events, 7.7% and 20.2% of the events were classified as probable and possible for embolism, respectively. Ceftazidime-calcium resulted in fewer probable embolic events (4%) but more possible embolic events (30.3%). Among cases that considered ceftriaxone or ceftazidime and calcium as the primary or secondary drug, one case was classified as a probable embolic event. That patient received ceftriaxone-calcium and died, although an attribution of causality was not possible. Our analysis suggests a lack of support for the occurrence of ceftriaxone-calcium precipitation events in adults. The results of the current analysis reinforce the revised FDA recommendations suggesting that patients >28 days old may receive ceftriaxone and calcium sequentially and provide a transparent and reproducible methodology for such evaluations.

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“…In addition, ceftriaxone was the most rapidly bactericidal agent within the cerebrospinal fluid (CSF) in vivo when it was compared with moxalactam, cefotaxime, ampicillin, and netilmicin in experimental animal models of meningitis induced by Escherichia coli, Streptococcus agalactiae, Streptococcus pneumoniae, or H. influenzae (9,11,24,34; Scheld et al, in press). Although the ceftriaxone concentrations in CSF are only a small fraction (-3 to 9%) of the concurrent serum concentrations, the bactericidal activity of this agent in CSF routinely exceeds the 90% MBC (MBC90) for the most common meningeal pathogens (5,13,20,21,26,35; Scheld et al, in press).…”

mentioning

confidence: 99%

Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis

Bryan¹,

Rocha²,

Silva³

et al. 1985

Antimicrob Agents Chemother

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Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were .0.06 to 0.25 j.Lg/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 ,ug/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8-to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to >1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined.Bacterial meningitis remains a relatively common disease worldwide. The recent emergence of pneumococci resistant to penicillin or chloramphenicol or both (18,27), the emergence of Haemophilus influenzae strains resistant to ampicillin or chloramphenicol or both (16,32,44,45), the continued high mortality due to gram-negative bacillary meningitis despite therapy with aminoglycosides or chloramphenicol or both (7), and the potential toxicity of chloramphenicol have all prompted the search for alternative agents for the therapy of meningitis.Ceftriaxone (RO13-9904) is a new third-generation cephalosporin with excellent in vitro activity against all major meningeal pathogens (1, 14, 17, 28, 39; Scheld, Rocha, Sande, and Bryan, Am. J. Med., in press), except Listeria monocytogenes. In addition, ceftriaxone was the most rapidly bactericidal agent within the cerebrospinal fluid (CSF) in vivo when it was compared with moxalactam, cefotaxime, ampicillin, and netilmicin in experimental animal models of meningitis induced by Escherichia coli, Streptococcus agalactiae, Streptococcus pneumoniae, or H. influenzae (9,11,24,34; Scheld et al., in press). Although the ceftriaxone concentrations in CS...

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Ceftriaxone pharmacokinetics in newborn infants

Cited by 41 publications

References 5 publications

Ceftriaxone Kinetics and Cerebrospinal Fluid Penetration in Infants and Children with Meningitis

Ceftriaxone Kinetics and Cerebrospinal Fluid Penetration in Infants and Children with Meningitis

Evaluation of a Potential Clinical Interaction between Ceftriaxone and Calcium

Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis

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