Journal of clinical pharmacology
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Multicenter Study Clinical Trial
Pharmacokinetics of hydrocodone/acetaminophen combination product in children ages 6-17 with moderate to moderately severe postoperative pain.
Lortab® Elixir, a proprietary combination product containing hydrocodone and acetaminophen, is approved in the US for the treatment of moderate to moderately severe pain in children. Despite this approval, pediatric pharmacokinetic data using this product have not been previously published. Using a single-dose open-label study approach, we evaluated the pharmacokinetics, tolerability, and safety of this product in 17 healthy children 6-17 years of age. ⋯ We found adjustment of hydrocodone and acetaminophen dose by body surface area to be more optimal than body weight-based dose adjustments for achieving similar systemic exposure in children and adults. However, body weight-based hydrocodone and acetaminophen dosing regimens provided close approximation of adult exposures in pediatric patients with approximately 22% to 24% lower hydrocodone and acetaminophen dose/BW-normalized AUC in pediatric patients compared to adults. Finally, the adverse event profile in our pediatric cohort was consistent with that expected of opioid-naive subjects receiving opioid-combination therapy.
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Multicenter Study Controlled Clinical Trial
Population pharmacokinetics of ceftolozane/tazobactam in healthy volunteers, subjects with varying degrees of renal function and patients with bacterial infections.
Ceftolozane/tazobactam is a novel antipseudomonal cephalosporin and β-lactamase inhibitor in clinical development for treatment of complicated urinary tract (cUTI) and intra-abdominal (cIAI) infections and nosocomial pneumonia. The population pharmacokinetics of ceftolozane/tazobactam were characterized in healthy volunteers, subjects with varying degrees of renal function, and patients with cIAI or cUTI. Serum concentration data from 376 adults who received ceftolozane/tazobactam in doses ranging from 500 to 3000 mg were analyzed to identify factors contributing to the pharmacokinetic variability. ⋯ Body weight was an additional covariate affecting the Vc of ceftolozane. Other covariates tested, such as age, body weight, sex, ethnicity, and presence of infection, had no clinically relevant effects on exposure. The final pharmacokinetic models adequately described the plasma concentrations of ceftolozane and tazobactam and form the basis for further modeling and simulation including evaluation of probability of target attainment in a diverse population with varying demographics, degrees of renal function, and infection status.