Tobramycin pharmacokinetic and pharmacodynamic targets in people with cystic fibrosis.

内容摘要

Intravenous tobramycin is a first-line treatment for Pseudomonas aeruginosa infection in people with cystic fibrosis (CF). Tobramycin exhibits concentration-dependent activity; however, excess drug exposure can lead to nephrotoxicity and ototoxicity. While dosing typically targets serum peak (Cmax) and trough (Cmin) concentrations, the area under the concentration-time curve over 24&#x2009;h (AUC24) is also used to guide therapy. However, optimal exposure targets remain unclear, leading to variability in clinical practice and guidelines. This review aimed to determine the target tobramycin concentrations and exposure (Cmax, Cmin, AUC24) associated with clinical efficacy (lung function improvement) and/or toxicity (nephrotoxicity, ototoxicity) in CF. Four databases (PubMed, Medline, Embase and Cochrane) were searched and identified studies involving CF patients receiving intravenous tobramycin, recorded tobramycin drug concentration/exposure alongside either clinical efficacy or drug-related toxicity outcomes. Studies with &#x2264;10 patients, in vitro studies and reviews were excluded. The Newcastle-Ottawa Scale was used to assess risk of bias. A meta-analysis was not conducted. Twenty-six studies were included; efficacy was reported in 17, nephrotoxicity in 16 and ototoxicity in 17. Both Cmax and AUC24 were associated with efficacy, with AUC24 being the more reliable predictor. Cmin and AUC24 were associated with toxicity. Only 11 studies reported AUC24, and the overall quality of evidence was poor (21 with medium/high risk of bias, 5 low bias). Current therapeutic Cmax (20-40&#x2009;mg/L) and Cmin (<1&#x2009;mg/L) targets remain appropriate. Evidence suggests AUC24-guided dosing for improved efficacy and safety; however, further research is needed to confirm the optimal AUC24 target (80-120&#x2009;mg/L&#xb7;h).