ORIGINAL ARTICLE The efficacy and toxicity of two dosing-regimens of amikacin in neonates with sepsis E. Abdel-Hady* MSc, M. El Hamamsy* PhD, M. Hedaya PhD and H. AwadàMD, FRCP, FRCPch *Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo,  Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta and àDepartment of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt SUMMARY What is known and objective: Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries. Amino- glycosides widely used in its treatment are usu- ally administered two or three times a day. Less frequent doing may be more convenient and as effective. We aim to compare the efficacy and safety (nephrotoxicity) of once daily vs. twice daily dosing of amikacin in neonates with sus- pected or proven sepsis and report on the drug’s pharmacokinetics in these subjects. Methods: Thirty neonates of gestational age ‡36 weeks and body weight ‡2500 g with sus- pected or proven sepsis were randomized to receive amikacin either at a dose of 15 mg ⁄ kg once per day; group I (n = 15), or a dose of 7Æ5 mg ⁄ kg twice per day, group II (n = 15). All neonates received classical treatment of sepsis including antibiotics, hemodynamic support, inotropic support based on blood pressure levels and size of the heart in chest X-ray, if needed. Amikacin was infused over 1 h. Peak and trough serum samples for amikacin were measured for all infants at steady state. Nephrotoxicity was assessed by serum creatinine and urinary N-acetyl b-D-glucosaminidase before and 7 days after therapy. Clinical efficacy was compared using both observation of clinical status and normali- zation of laboratory tests. Results: All the patients in group I had achieved a trough level <10 lg ⁄ mL and two patients had trough concentration >10 lg ⁄ mL in group II. No significant difference between group I and group II in either baseline or day 7 serum creatinine was demonstrated (P >0Æ05). No significant difference was found between the two groups in clinical efficacy or renal toxicity. The calculated pharma- cokinetic parameters were in group I and II, respectively: clearance = 63Æ8 ± 15Æ9 mL ⁄ kg ⁄ h and 73Æ5 ± 18Æ1 mL ⁄ kg ⁄ h; volume of distribution = 0Æ54 ± 0Æ09 L ⁄ kg and 0Æ61 ± 0Æ13 L ⁄ kg, half-life = 6Æ1±1Æ0 h and 5Æ95 ± 1Æ1 h. What is new and conclusion: As expected, ami- kacin given once every 24 h to septic neonates of ‡36 weeks of gestation achieved higher peak levels and lower trough concentrations than the twice daily regimen. Treatment with once daily regimen did not lead to more nephrotoxicity than with a twice-daily regimen, and showed compa- rable efficacy. Keywords: amikacin, efficacy, neonatal sepsis, nephrotoxicity, once daily, twice daily INTRODUCTION Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries (1). Neonatal sepsis can be classified into two relatively distinct illnesses based on the post- natal age at onset; early onset sepsis (EOS) usually presenting within the first 72 h of life (2) and late onset sepsis (LOS) that usually presents after 72 h of age (3). Clinical signs and symptoms of sepsis are non-specific making diagnosis particularly chal- lenging to physicians. These signs and symptoms Received 1 August 2009, Accepted 11 November 2009 Correspondence: E. Abdel-Hady, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Tel.: +202 22529677; fax: +202 24051107; e-mail: engi_ph@yahoo.com Journal of Clinical Pharmacy and Therapeutics (2011) 36, 45–52 doi:10.1111/j.1365-2710.2009.01152.x Ó 2010 Blackwell Publishing Ltd 45