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Pharmacokinetics and safety of ceftriaxone in the neonate

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Abstract

The pharmacokinetics and safety of ceftriaxone were examined in 39 neonates who required antibiotics for clinically suspected sepsis. The drug was administered as a once daily dose of 50 mg/kg by the intravenous (IV) or intramuscular (IM) route. Ceftriaxone was assayed in 49 series of blood samples, 3 samples of cerebrospinal fluid (CSF) and 15 samples of urine by a microbiological technique. Blood was collected before, during and after treatment for biochemical analysis. Routine haematological investigations were also monitored. There was no significant differences between the maximum plasma concentrations following IV (153±39 mg/l) or IM (141±19 mg/l) administration (first dose). The mean elimination half-life, total body clearance, and volume of distribution following the first dose were 15.4±5.4 h, 0.28±0.12 ml/min per kg and 325±59 ml/kg respectively. Clearance increased with increasing postnatal age and body temperature (P<0.0002) and decreasing plasma creatinine concentration (P<0.005). Increasing plasma protein concentration was associated with a decrease in volume of distribution (P<0.001). There were no drug-associated changes in any of the biochemical or haematological parameters examined. Ceftriaxone is a safe and well tolerated antibiotic for use in the treatment of newborn sepsis and possibly meningitis. A once daily administration of 50 mg/kg by the IV and IM routes provides satisfactory plasma concentrations throughout the dosage interval whilst avoiding accumulation.

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Abbreviations

IV:

intravenous

IM:

intramuscular

CSF:

cerebrospinal fluid

Cmax:

maximum, serum concentration

T1/2β:

serum elimination half-life

Cl:

total body clearance

Vd:

volume of distribution

Tmax:

time to maximum serum concentration

References

  1. 1.

    Bint AJ, Yeoman P, Kilburn P, Anderson R, Stansfield E (1981) The in vitro activity of ceftazidime compared with that of other cephalosporins. J Antimicrob Chemother 8:[Suppl B] 47–51

  2. 2.

    Childs SJ (1983) Bleeding problems. Arch Intern Med 143:183

  3. 3.

    de Louvois J, Mulhall A, Hurley R (1982) Cefuroxime in the treatment of neonates. Arch Dis Child 57:59–62

  4. 4.

    de Louvois J, Mulhall A, James J (1983) Latamoxef as an alternative to gentamicin in the treatment of clinically infected neonates. Proceedings of the 13th International Congress of Chemotherapy, Vienna, part 67:16–19

  5. 5.

    Del Rio MA, McCracken GH, Nelson JD, Chrane DF (1981) Pharmacokinetics of cefuroxime and ceftriaxone in serum and cerebrospinal fluid of patients with bacterial meningitis. Abstract 392. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago

  6. 6.

    Gould Chadwick E, Yogev R, Shulman ST, Weinfield RE, Patel IH (1983) Single dose ceftriaxone pharmacokinetics in paediatric patients with central nervous system infections. J Pediatr 102:134–137

  7. 7.

    Greenblatt DJ, Koch-Weser J (1975) Clinical pharmacokinetics. N Engl J Med 293:702–705, 964–970

  8. 8.

    Marchou B, Van Tho T, Armengaud M (1981) Diffusion of ceftriaxone (Ro 13-9904/001) in the cerebrospinal fluid. Comparison with other beta-lactam antibiotics in dogs with healthy meninges and in dogs with experimental meningitis. Chemotherapy 27 [Suppl 1]:37–41

  9. 9.

    McCracken GH Jr, Siegel JD, Threlkeld N, Thomas M (1983) Ceftriaxone pharmacokinetics in newborn infants. Antimicrob Agents Chemoth 23:341–343

  10. 10.

    Neu HC (1982) The in vitro activity, human pharmacology and clinical effectiveness of new β-lactam antibiotics. Annu Rev Pharmacol Toxicol 22:599–642

  11. 11.

    Reiner R, Weiss U, Brombacher U, Lanx P, Montavon M, Furlenmeier A, Angehrn P, Probst PJ (1980) R-13-9904-001, a novel potent and long acting parenteral cephalosporin. J Antibiot (Tokyo) 33:783–786

  12. 12.

    Schaad UB, McCracken GH Jr, Loock CA, Thomas ML (1981) Pharmacokinetics and bacteriologic efficacy of moxalactam, cefotaxime, cefoperazone and Rocephin in experimental bacterial meningitis. J Infect Dis 143:156–163

  13. 13.

    Schaad UB, Stoeckel K (1982) Single dose pharmacokinetics of ceftriaxone in infants and young children. Antimicrob Agents Chemother 21:248–253

  14. 14.

    Schaad UB, Stoeckel K (1983) Pharmacokinetics of ceftriaxone in paediatric patients. Abstract 30, European Society for Pediatric Research, Montpellier

  15. 15.

    Scully B, Neu HC (1981) The human pharmacology of ceftriaxone. Abstract 805, Interscience conference on Antimicrobial Agents and Chemotherapy (ICAAC) Chicago

  16. 16.

    Seddon M, Wise R, Gillett AP, Livingston R (1980) Pharmacokinetics of Ro-13-9904, a broad spectrum cephalosporin. Antimicrob Agents Chemother 18:240–242

  17. 17.

    Sedman AJ, Wagner JG (1976) CSTRIP, a Fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 65:1006–1010

  18. 18.

    Stoeckel K (1983) Pharmacokinetics of ceftriaxone, a long acting broad spectrum cephalosporin. “Proceedings Progress in therapy of bacterial infections. A new cephalosporin: Ceftriaxone.” Bangkok, Thailand. Excerpta Med, Asia Pacific Congress Series No 19, P5, 1983

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Correspondence to A. Mulhall.

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Mulhall, A., de Louvois, J. & James, J. Pharmacokinetics and safety of ceftriaxone in the neonate. Eur J Pediatr 144, 379–382 (1985). https://doi.org/10.1007/BF00441782

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Key words

  • Ceftriaxone
  • Neonate
  • Pharmacokinetics
  • Safety