Pharmacokinetics of Ceftriaxone in Pediatric Patients With Meningitis

Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 03/1983; 23(2):191-4. DOI: 10.1128/AAC.23.2.191
Source: PubMed


Pharmacokinetics of ceftriaxone after a single dose of 50 or 75 mg/kg were determined in 30 pediatric patients with bacterial
meningitis. Data for doses of 50 and 75 mg/kg, respectively, were as follows (mean ± standard deviation): maximum plasma concentrations,
230 ± 64 and 295 ± 76 μg/ml; elimination rate constant, 0.14 ± 0.06 and 0.14 ± 0.04 h−1; harmonic elimination half-life, 5.8 ± 2.8 and 5.4 ± 2.1 h; plasma clearance, 51 ± 24 and 55 ± 18 ml/h per kg; volume of
distribution, 382 ± 129 and 387 ± 56 ml/kg; mean concentration in cerebrospinal fluid 1 to 6 h after infusion, 5.4 and 6.4
μg/ml. A dosage schedule of 50 mg/kg every 12 h for bacterial meningitis caused by susceptible organisms is suggested for
pediatric patients over 7 days of age.

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Available from: Robert W Bradsher, Apr 03, 2015
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    • "The intravenous and intramuscular administration of ceftriaxone yielded similar kinetic parameters [50]. Steele et al. [51] observed that the peak concentration of ceftriaxone was higher after 75 than after 50 mg/kg. Cl ranged from 0.28 to 0.93 mL/min/kg, Vd ranged between 0.32 and 0.57 L/kg and t1/2 ranged from 5.2 and 16.2 h. "
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    ABSTRACT: Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.
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    ABSTRACT: Ceftriaxone, a new third-generation cephalosporin, appearstobepromising forthetherapy ofacute bacterial meningitis. The90% MBCs ofceftriaxone against 54 recentcerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, andHaemophilus influenzae were .0.06 to0.25j.Lg/ml. We examined theefficacy andsafety ofceftriaxone therapy ofmeningitis inBahia, Brazil. Thestudy wasconducted intwophases; inphaseA,ceftriaxone was coadministered withampicillin. Themean cerebrospinal fluid concentrations ofceftriaxone 24hafter an intravenous doseof80mg/kgwere4.2and2.3,ug/ml on days4to 6and10to12oftherapy, respectively. Theseconcentrations were 8-tomore than100-fold greater thanthe 90%MBCs against therelevant pathogens. InphaseB,ceftriaxone (administered oncedaily ata doseof80 mg/kgafter an initial doseof100mg/kg) was compared withconventional dosages ofampicillin and chloramphenicol inaprospective randomized trial of36children andadults withmeningitis. Thegroupswere comparable based on clinical, laboratory, andetiological parameters. Ceftriaxone given oncedaily produced results equivalent tothose obtained withampicillin pluschloramphenicol, asjudged bycurerate, casefatality ratio, resolution withsequelae, typeandseverity ofsequelae, timetosterility ofcerebrospinal fluid, and potentially drug-related adverse effects. Thecerebrospinal fluid bactericidal titers obtained 16to24hafter ceftriaxone dosing were usually 1:512 to>1:2,048 evenlate inthetreatment course,compared withvalues of 1:8to1:32inpatients receiving ampicillin pluschloramphenicol. Ceftriaxone clearly deserves further evaluation forthetherapy ofmeningitis; theoptimal dose, dosing frequency (every 12hor every24h),and duration oftherapy remaintobedetermined.
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