Altered Gentamicin Serum Concentrations in Obese Pediatric Patients

Choi, Jamie J.; Moffett, Brady S.; McDade, Erin; Palazzi, Debra L.

doi:10.1097/inf.0b013e3181ff023e

Cited by 38 publications

(29 citation statements)

References 8 publications

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“…Increased amounts of adipose tissue in a patient can potentially result in increased serum concentrations, and subsequent adverse events, of water-soluble medications. 2,3 There is limited information on the effects of obesity on the pharmacokinetics of drugs, with even more limited recommendations, particularly in pediatrics. 4,5 Fosphenytoin is the water-soluble pro-drug of phenytoin, which is commonly used in the treatment of seizures in pediatric patients.…”

Section: Introductionmentioning

confidence: 98%

Impact of Body Habitus on Phenytoin Levels Following Fosphenytoin Loading Dose in Pediatric Patients

Messinger

Moffett

Wilfong³

2015

Therapeutic Drug Monitoring

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Section: Introductionmentioning

confidence: 98%

Impact of Body Habitus on Phenytoin Levels Following Fosphenytoin Loading Dose in Pediatric Patients

Messinger

Moffett

Wilfong³

2015

Therapeutic Drug Monitoring

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“…The remaining 20 publications contained PK data for 21 drugs, including 7 anti-neoplastic drugs, 4 anticonvulsants, 4 antibiotics, 3 analgesic/anesthetic drugs, 2 respiratory stimulants, and 1 immunosuppressant (Table 1). Six out of 21 (29%) drugs were not studied in a formal prospective PK trial (gentamicin 29 ; vancomycin 17,18,30 ; valproic acid 19 ; divalproex sodium 20 ; busulfan 21 ; and cyclosporine 36 ). PK data for these studies were collected following drug administration per standard of care, frequently with sparse sampling.…”

Section: Resultsmentioning

confidence: 99%

Drug Dosing and Pharmacokinetics in Children With Obesity

et al. 2015

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IMPORTANCE-Obesity affects nearly one sixth of U.S. children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxicity. The depth of available literature regarding obesity's effect on drug safety, pharmacokinetics (PK) and dosing in obese children is unknown.OBJECTIVE-To perform a systematic literature review describing the current evidence of the effect of obesity on drug disposition in children. EVIDENCE REVIEW-We searched the Medline, Cochrane, and Embase databases (January 1970-December 2012 and included studies if they contained clearance, volume of distribution, or drug concentration data in obese children (age ≤18 years). We compared exposure and weightnormalized volume of distribution and clearance between obese and non-obese children.

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“…Gentamicin was studied in a retrospective cohort study in 25 obese and 25 non-obese children with a mean ± standard deviation age of 9.9 ± 3.9 years and obese children’s BMI percentile of 98 ± 1.3 [31]. Obese children received significantly lower TBW-normalized doses relative to their non-obese peers (mean 1.86 vs. 2.25 mg/kg TBW, p<0.01), had significantly higher peak concentrations (8.17 ± 2.02 vs. 7.06 ± 1.52 µg/mL, p<0.05), similar trough concentrations (0.95 ± 0.58 vs. 0.74 ± 0.24 µg/mL, p=0.11), and decreased weight-normalized V (0.20 ± 0.05 vs. 0.28 ± 0.07 L/kg TBW, p<0.01).…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of antimicrobials in obese children

Sampson

Cohen‐Wolkowiez

Benjamin

et al. 2013

GaBI J

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Introduction Childhood obesity is common and results in substantial morbidity. The most commonly prescribed drugs in obese children are antibiotics. However, physiologic changes associated with childhood obesity can alter antibiotic pharmacokinetics and optimal body size measures to guide dosing in his population are ill defined. This combination can result in therapeutic failures or drug-related toxicities. This review summarizes pharmacokinetic information for antibiotics in obese children and implications for dosing. Methods We conducted a comprehensive literature search of PubMed, EMBASE, and International Pharmaceutical Abstracts to identify pharmacokinetic studies of antimicrobial agents in obese children. We included the following search terms: obesity, pharmacokinetics, pharmacodynamics, drug toxicity, dosing, anti-infective agents, antiviral agents, and antifungal agents. Results We identified four pharmacokinetic studies of antibiotics in obese children: one for cefazolin and tobramycin, one for gentamicin, and two for vancomycin. Only the cefazolin/tobramycin trial was prospective. The drugs studied differ in their tissue and body water distribution characteristics. Two of the studies (tobramycin and gentamicin) reported pharmacokinetic differences and required dosing modifications in obese children. Discussion The lack of pharmacokinetic studies in obese children is pronounced. The scarcity of pharmacokinetic data limits the ability to predict drug disposition using drug physicochemical properties and impedes a rational approach to selection of appropriate body size measures for dosing. Given this knowledge gap, additional trials in obese children are urgently needed and is a public health concern. Conclusion Pharmacokinetic studies of antimicrobials in obese children are desperately needed to guide dosing and avoid therapeutic failures or unwanted toxicities.

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Altered Gentamicin Serum Concentrations in Obese Pediatric Patients

Cited by 38 publications

References 8 publications

Impact of Body Habitus on Phenytoin Levels Following Fosphenytoin Loading Dose in Pediatric Patients

Impact of Body Habitus on Phenytoin Levels Following Fosphenytoin Loading Dose in Pediatric Patients

Drug Dosing and Pharmacokinetics in Children With Obesity

Pharmacokinetics of antimicrobials in obese children

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