Amikacin Therapy in Japanese Pediatric Patients: Narrative Review
Hideo Kato1,2, Yukihiro Hamada3
1Department of Pharmacy, Mie University Hospital, Tsu 514-8507, Japan.
Insights
This review highlights the need for more pharmacokinetic studies on amikacin in Japanese children. Optimal minimum concentrations (Cmin) may be below 10 mg/L, but further research on concentration-response is vital.
Area of Science:
- Pediatric Pharmacology
- Drug Metabolism and Pharmacokinetics
- Infectious Diseases
Background:
- Pediatric patients exhibit significant pharmacokinetic variability due to developmental changes.
- Existing pharmacokinetic data predominantly originates from Caucasian populations, limiting applicability to other ethnicities.
- The impact of developmental changes on amikacin pharmacokinetics and exposure-response in Japanese children is not well-established.
Purpose of the Study:
- To review existing literature on amikacin therapy in Japanese pediatric patients.
- To explore the relationship between amikacin concentrations, efficacy, and toxicity.
- To identify gaps in knowledge regarding amikacin pharmacokinetics in this population.
Main Methods:
- A narrative review of ten relevant articles was conducted.
- Data extraction focused on amikacin maximum concentration (Cmax) and minimum concentration (Cmin).
- Analysis included reported efficacy, toxicity, and, where available, pharmacokinetic/pharmacodynamic (PK/PD) indices and minimum inhibitory concentrations (MIC).
Main Results:
- Most identified studies were published in the 1980s.
- All patients achieved clinical recovery and negative cultures.
- A Cmin above 10 mg/L was associated with toxicity in three of four affected patients, though the number of toxic events was small.
Conclusions:
- Further pharmacokinetic studies of amikacin in Japanese pediatric patients are essential.
- Investigating the Cmax/MIC ratio is crucial for optimizing amikacin therapy.
- A Cmin below 10 mg/L is proposed as a potential target concentration, pending further investigation.
Abstract:
Children show a very wide range of physical development processes. These changes impact pharmacokinetic (PK) variability in pediatric patients. Most PK studies have been conducted on the Caucasian population. Therefore, whether current evidence of how developmental change affects PK and exposure-response relationships applies to Japanese pediatric patients remains unclear. This narrative review focuses on amikacin therapy in Japanese pediatric patients and shows the relationship between amikacin concentrations and efficacy/toxicity. Ten relevant articles were identified. Of these, nine articles were published in the 1980s. All studies reported a maximum concentration (Cmax) and minimum concentration (Cmin) of amikacin. Overall, articles reporting PK/pharmacodynamic (PD) indices and minimum inhibitory concentration (MIC) of isolated bacteria in Japanese pediatric patients is lacking, whereas all patients recovered from an infection state and showed negative cultures. Five of the included studies reported the association between Cmin and toxicity. The Cmin in three of four patients who developed toxicity was above 10 mg/L. This narrative review shows that further PK study of amikacin in Japanese pediatric patients is necessary. In particular, the pursuit of knowledge of Cmax/MIC ratio is vital. On the other hand, this review demonstrates that the optimal Cmin for Japanese pediatric patients is below 10 mg/L as a candidate concentration. However, it is noted that the number of patients who developed toxicity is very small.
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