Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

Knoderer, Chad A.; Saft, Sarah A.; Walker, Scott G.; Rodefeld, Markl D.; Turrentine, Mark W.; Brown, John W.; Healy, Daniel P.; Sowinski, Kevin M.

doi:10.1053/j.jvca.2010.07.022

Cited by 23 publications

(26 citation statements)

References 33 publications

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“…However, these results differ from other pharmacokinetic studies for cefuroxime sodium in humans, rats and goats that observed that a bi-compartmental model provided the best fit [19][20][21][22] . The reasons for this disparity may be related to interspecies variation, health status, or assay method employed [23] .…”

Section: Wwwchinapharcom Zhao Ls Et Alcontrasting

confidence: 99%

Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats

et al. 2012

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Aim:To compare the pharmacokinetic parameters of cefuroxime lysine, a new second-generation of cephalosporin antibiotics, after intravenous (IV), intraperitoneal (IP), or intramuscular (IM) administration. Methods: Twelve male and 12 virgin female Sprague-Dawley rats, weighing from 200 to 250 g, were divided into three groups (n=4 for each gender in each group). The rats were administered a single dose (67.5 mg/kg) of cefuroxime lysine via IV bolus or IP or IM injection. Blood samples were collected and analyzed with a validated UFLC-MS/MS method. The concentration-time data were then calculated by compartmental and non-compartmental pharmacokinetic methods using DAS software. Results: After IV, IP or IM administration, the plasma cefuroxime lysine disposition was best described by a tri-compartmental, bi-compartmental or mono-compartmental open model, respectively, with first-order elimination. The plasma concentration profiles were similar through the 3 administration routes. The distribution process was rapid after IV administration: the value of t 1/2(d) was 0.10±0.11 h, 1.36±0.65 h, and 1.25±1.01 h after IV, IP or IM administration. The AUMC 0-∞ is markedly larger, and mean residence time (MRT) is greatly longer after IP administration: the value of AUMC 0-∞ was 16.84±4.85, 55.33±20.34, and 36.17±13.24 mg·h 2 /L; the value of MRT was 0.37±0.07 h, 0.93±0.10 h, and 0.65±0.05 h after IV, IP or IM administration. The C max after IM injection was significantly higher than that in IP injection (73.51±12.46 vs 49.09±7.06 mg/L). There was no significantly sex-related difference in other pharmacokinetic parameters of cefuroxime lysine between male and female rats, except the value of AUC 0-∞ via IM administration that was significantly larger in male rats than that in female rats (66.38±16.5 vs 44.23±6.37 mg·h/L). Conclusion: Cefuroxime lysine shows quick absorption after IV injection, a long retension after IP injection, and a high C max after IM injection. After IM administration the AUC 0-∞ in male rats was significantly larger than that in female rats.

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Section: Wwwchinapharcom Zhao Ls Et Alcontrasting

confidence: 99%

Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats

et al. 2012

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“…Nascimento et al [14] reported a volume of distribution (V D ) of 0.19, 0.25 and 0.22 L/kg (mean 0.22 L/kg), which matched the V D of 0.21 L/kg (range 0.081 – 0.423 L/kg) reported by Knoderer et al [12]. Powell et al reported a half-life (t 1/2 ) of 1.9, 1.4, and 1.9 h (mean 1.75 h) which was similar to the t 1/2 of 1.8 h reported by del Rio et al [15, 17].…”

Section: Methodsmentioning

confidence: 52%

“…An elimination coefficient of 0.693/1.75 h or 0.396 per hour was used for in silico plasma concentration-time simulations following intravenous (IV) cefuroxime 25 mg/kg and 50 mg/kg doses. The V D range of 0.081 – 0.423 L/kg reported by Knoderer et el [12] was used to simulate priming volumes, where 0.08 represented a priming volume of zero (mL/kg) and the upper range of 0.43 L/kg represented a priming volume of 350 mL/kg (0.43 minus 0.08 L/kg = 0.35 L/kg or 350 mL/kg). Simulations were run using Phoenix WinNonLin 6.2.1.51, Sunnyvale, CA.…”

Section: Methodsmentioning

confidence: 93%

Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

Huang

Sunstrom

Munar

et al. 2014

The Journal of Thoracic and Cardiovascular Surgery

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OBJECTIVES Perioperative antibiotics have decreased, but not eradicated post-operative infections. In patients undergoing cardiac surgery with cardiopulmonary bypass, the dilutional effect of the priming and any additional volume given during the procedure may lead to subtherapeutic antibiotic levels. Our aim was to determine whether children undergoing cardiac surgery with cardiopulmonary bypass receive subtherapeutic perioperative antibiotics. METHODS Using published pharmacokinetic data on cefuroxime, we developed a computer simulation model to generate a nomogram predicting patients at risk for subtherapeutic cefuroxime levels based on time from initial dosing and additional volume given. RESULTS A computer-generated one-compartment pharmacokinetic model was created predicting cefuroxime plasma levels over time for patients of all weights and additional volumes given for both a 25- and 50 mg/kg intravenous dose. For example, following a 25 mg/kg dose, a subject receiving an additional volume of 275 mL/kg is predicted to be subtherapeutic (<16 mg/L = 4 x mininum inhibitory concentration) at 4 hours. Our nomogram predicts all subjects will be subtherapeutic at 8 hours consistent with general pediatrics dosing schemes. Following a 50 mg/kg dose, levels are predicted to be subtherapeutic after an additional volume of 315 ml/kg at 5.5 hours. CONCLUSION Our model predicts which patients undergoing cardiac surgery with cardiopulmonary will have subtherapeutic cefuroxime levels. This nomogram enables providers to determine when to re-dose antibiotics in patients receiving large additional volumes during cardiac surgeries. This rational approach to perioperative antibiotic dosing may result in a reduction in post-operative infection in this vulnerable patient population.

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“…PK of cefotaxime during ECMO and of cefuroxime during CPB is altered but plasma levels are more than the MIC using normal dosing regimens. 101,102 Cefotaxime Cl was found to be increased during ECMO compared with the pre-ECMO and post-ECMO period, possibly reflecting improved hepatic or renal perfusion during ECMO or Cl via hemofiltration. 101 A possible decrease in Cl caused by hypothermia increases plasma levels, negating the effects of ECMO.…”

Section: Introductionmentioning

confidence: 92%

The Impact of Extracorporeal Life Support and Hypothermia on Drug Disposition in Critically Ill Infants and Children

Wildschut¹,

Saet²,

Pokorná³

et al. 2012

Pediatric Clinics of North America

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Cefuroxime Pharmacokinetics in Pediatric Cardiovascular Surgery Patients Undergoing Cardiopulmonary Bypass

Cited by 23 publications

References 33 publications

Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats

Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats

Are children undergoing cardiac surgery receiving antibiotics at subtherapeutic levels?

The Impact of Extracorporeal Life Support and Hypothermia on Drug Disposition in Critically Ill Infants and Children

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