Limited sampling strategies for therapeutic drug monitoring of amikacin and kanamycin in patients with multidrug-resistant tuberculosis

作者：Dijkstra J A; van Altena R; Akkerman O W; de Lange W C M; Proost J H; van der Werf T S; Kosterink J G W; Alffenaar J W C^*

来源：International Journal of Antimicrobial Agents, 2015, 46(3): 332-337.

DOI：10.1016/j.ijantimicag.2015.06.008

• Amikacin
• Kanamycin
• Tuberculosis
• Pharmacokinetics
• Pharmacokinetic model
• Limited sampling

Amikacin and kanamycin are considered important and effective drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). Unfortunately, the incidence of toxicity is high and is related to elevated drug exposure. In order to achieve a balance between efficacy and toxicity, a population pharmacokinetic (PPK) model may help to optimise drug exposure. Patients with MDR-TB who had received amikacin or kanamycin as part of their treatment and who had routinely received therapeutic drug monitoring were evaluated. A PPK model was developed and subsequently validated. Using this model, a limited sampling model was developed. Eleven patients receiving amikacin and nine patients receiving kanamycin were included in this study. The median observed 24-h area under the concentration-time curve (AUC(0-24h)) was 77.2 mg h/L [interquartile range (IQR) 64.7-96.2 mg h/L] for amikacin and 64.1 mg h/L (IQR 55.6-92.1 mg h/L) for kanamycin. The PPK model was developed and validated using n-1 cross-validation. A robust population model was developed that is suitable for predicting the AUC(0-24h) of amikacin and kanamycin. This model, in combination with the limited sampling strategy developed, can be used in daily routine to guide dosing but also to assess AUC0_24h in phase 3 studies.

• 出版日期2015-9