TY - JOUR
T1 - Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity
AU - on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
AU - Maharaj, Anil R.
AU - Wu, Huali
AU - Zimmerman, Kanecia O.
AU - Muller, William J.
AU - Sullivan, Janice E.
AU - Sherwin, Catherine M.T.
AU - Autmizguine, Julie
AU - Rathore, Mobeen H.
AU - Hornik, Chi D.
AU - Al-Uzri, Amira
AU - Payne, Elizabeth H.
AU - Benjamin, Daniel K.
AU - Hornik, Christoph P.
AU - Hornik, Christoph
AU - Zimmerman, Kanecia
AU - Kennel, Phyllis
AU - Beci, Rose
AU - Hornik, Chi Dang
AU - Kearns, Gregory L.
AU - Laughon, Matthew
AU - Paul, Ian M.
AU - Sullivan, Janice
AU - Wade, Kelly
AU - Delmore, Paula
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
PY - 2021/9
Y1 - 2021/9
N2 - Purpose: The aim of this study was to evaluate ceftazidime pharmacokinetics (PK) in a cohort that includes a predominate number of children and adolescents with obesity and assess the efficacy of competing dosing strategies. Methods: A population PK model was developed using opportunistically collected plasma samples. For each dosing strategy, model-based probability of target attainment (PTA) estimates were computed for study participants using empirical Bayes estimates. In addition, the effects of body size and renal function on PTA were evaluated using stochastic model simulations with virtually generated subjects. Results: Twenty-nine participants, 24 of whom were obese, contributed data towards the analysis. The median (range) age, body weight, and body mass index of participants were 12.2 years (2.3–20.6), 59.2 kg (8.4–121), and 25.2 kg/m2 (13.8–42.9), respectively. Administration of 50 mg/kg intravenously (IV) every 8 hours (q8h; max 6 g/day) or 40 mg/kg IV q6h (max 6 g/day) resulted in PTA values of ≥ 90% (minimum inhibitory concentration 8 mg/L) for the subset of obese participants with estimated glomerular filtration rates (GFR) ≥ ~ 80 mL/min/1.73 m2. However, for both regimens, stochastic model simulations denoted lower PTA values (< 90%) with increasing body weight for virtual subjects with GFR ≥ 120 mL/min/1.73 m2. Alternatively, permitting for a maximum daily dose of 8 g/day using a 40 mg/kg IV q6h regimen provided PTA values that were near or above target (90%) for virtual subjects between 10 to 120 kg with GFR ≥ 80 mL/min/1.73 m2. Conclusion: Our analysis suggests administration of 40 mg/kg IV q6h (max 8 g/day) maximizes PTA in children and adolescents with obesity and GFR ≥ 80 mL/min/1.73 m2. Trial Registration: Clinicaltrials.gov Identifier: NCT01431326.
AB - Purpose: The aim of this study was to evaluate ceftazidime pharmacokinetics (PK) in a cohort that includes a predominate number of children and adolescents with obesity and assess the efficacy of competing dosing strategies. Methods: A population PK model was developed using opportunistically collected plasma samples. For each dosing strategy, model-based probability of target attainment (PTA) estimates were computed for study participants using empirical Bayes estimates. In addition, the effects of body size and renal function on PTA were evaluated using stochastic model simulations with virtually generated subjects. Results: Twenty-nine participants, 24 of whom were obese, contributed data towards the analysis. The median (range) age, body weight, and body mass index of participants were 12.2 years (2.3–20.6), 59.2 kg (8.4–121), and 25.2 kg/m2 (13.8–42.9), respectively. Administration of 50 mg/kg intravenously (IV) every 8 hours (q8h; max 6 g/day) or 40 mg/kg IV q6h (max 6 g/day) resulted in PTA values of ≥ 90% (minimum inhibitory concentration 8 mg/L) for the subset of obese participants with estimated glomerular filtration rates (GFR) ≥ ~ 80 mL/min/1.73 m2. However, for both regimens, stochastic model simulations denoted lower PTA values (< 90%) with increasing body weight for virtual subjects with GFR ≥ 120 mL/min/1.73 m2. Alternatively, permitting for a maximum daily dose of 8 g/day using a 40 mg/kg IV q6h regimen provided PTA values that were near or above target (90%) for virtual subjects between 10 to 120 kg with GFR ≥ 80 mL/min/1.73 m2. Conclusion: Our analysis suggests administration of 40 mg/kg IV q6h (max 8 g/day) maximizes PTA in children and adolescents with obesity and GFR ≥ 80 mL/min/1.73 m2. Trial Registration: Clinicaltrials.gov Identifier: NCT01431326.
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U2 - 10.1007/s40272-021-00460-4
DO - 10.1007/s40272-021-00460-4
M3 - Article
C2 - 34302290
AN - SCOPUS:85111622573
SN - 1174-5878
VL - 23
SP - 499
EP - 513
JO - Pediatric Drugs
JF - Pediatric Drugs
IS - 5
ER -