European Journal of Pediatrics

, Volume 144, Issue 4, pp 379–382 | Cite as

Pharmacokinetics and safety of ceftriaxone in the neonate

  • A. Mulhall
  • J. de Louvois
  • J. James
Original Investigations

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.

Key words

Ceftriaxone Neonate Pharmacokinetics Safety 

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

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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] 47–51Google Scholar
  2. 2.
    Childs SJ (1983) Bleeding problems. Arch Intern Med 143:183Google Scholar
  3. 3.
    de Louvois J, Mulhall A, Hurley R (1982) Cefuroxime in the treatment of neonates. Arch Dis Child 57:59–62Google Scholar
  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 67:16–19Google Scholar
  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), ChicagoGoogle Scholar
  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 102:134–137Google Scholar
  7. 7.
    Greenblatt DJ, Koch-Weser J (1975) Clinical pharmacokinetics. N Engl J Med 293:702–705, 964–970Google Scholar
  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]:37–41Google Scholar
  9. 9.
    McCracken GH Jr, Siegel JD, Threlkeld N, Thomas M (1983) Ceftriaxone pharmacokinetics in newborn infants. Antimicrob Agents Chemoth 23:341–343Google Scholar
  10. 10.
    Neu HC (1982) The in vitro activity, human pharmacology and clinical effectiveness of new β-lactam antibiotics. Annu Rev Pharmacol Toxicol 22:599–642Google Scholar
  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) 33:783–786Google Scholar
  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 143:156–163Google Scholar
  13. 13.
    Schaad UB, Stoeckel K (1982) Single dose pharmacokinetics of ceftriaxone in infants and young children. Antimicrob Agents Chemother 21:248–253Google Scholar
  14. 14.
    Schaad UB, Stoeckel K (1983) Pharmacokinetics of ceftriaxone in paediatric patients. Abstract 30, European Society for Pediatric Research, MontpellierGoogle Scholar
  15. 15.
    Scully B, Neu HC (1981) The human pharmacology of ceftriaxone. Abstract 805, Interscience conference on Antimicrobial Agents and Chemotherapy (ICAAC) ChicagoGoogle Scholar
  16. 16.
    Seddon M, Wise R, Gillett AP, Livingston R (1980) Pharmacokinetics of Ro-13-9904, a broad spectrum cephalosporin. Antimicrob Agents Chemother 18:240–242Google Scholar
  17. 17.
    Sedman AJ, Wagner JG (1976) CSTRIP, a Fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 65:1006–1010Google Scholar
  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, 1983Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • A. Mulhall
    • 1
  • J. de Louvois
    • 1
  • J. James
    • 1
  1. 1.Queen Charlotte's Maternity HospitalLondonUK

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