Farhad Najmeddin1, Bita Shahrami1, Sayna Azadbakht2, Mehrnoush Dianatkhah1, Mohammad Reza Rouini3, Atabak Najafi4, Arezoo Ahmadi4, Hamidreza Sharifnia4, Mojtaba Mojtahedzadeh1,5. 1. Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 2. School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Anesthesiology and Critical Care, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. 5. Pharmaceutical Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
INTRODUCTION: Classically, aminoglycosides are known to have low penetration into the lung tissue. So far, no study has been conducted on human adult patients to evaluate amikacin concentration in epithelial lining fluid (ELF) of the alveoli. Therefore, convincing data are not available from the perspective of pharmacokinetics to support the fact that a dosage of 20 mg/kg of amikacin is sufficient to treat patients with ventilator-associated pneumonia (VAP). METHOD: This was a pilot study of amikacin concentration measurement in the alveolar site of action in critically ill adult patients with VAP who required aminoglycoside therapy. A dose of 20 mg/kg of amikacin was administered over a 30-minute infusion. The serum concentrations of amikacin were evaluated in the first, second, fourth, and sixth hours. However, the ELF concentration of amikacin was evaluated in the second hour with the help of bronchoalveolar lavage sampling technique. RESULTS: A total number of 8 patients was included in the study. The mean (SD) administered dose was 20 (0.9) mg/kg. The mean (SD) peak plasma concentration of amikacin was 59.6 (23) mg/L, with the volume of distribution of 0.36 (0.13)L/kg. The amikacin concentration in ELF was successfully measured in 7 patients (6.3) mg/L. The lung tissue penetration of the drug was described as alveolar percentage, proportional to both the first- and second-hour plasma concentrations, with a mean (SD) of 10.1% (8.4%) and 18% (16.7%), respectively. CONCLUSION: To our knowledge, the current study is the first that investigates whether standard doses of amikacin may lead to sufficient alveolar concentration of the drug. The results show that administration of amikacin in doses of 20 mg/kg in critically ill patients with VAP may not provide sufficient concentrations in ELF.
INTRODUCTION: Classically, aminoglycosides are known to have low penetration into the lung tissue. So far, no study has been conducted on human adult patients to evaluate amikacin concentration in epithelial lining fluid (ELF) of the alveoli. Therefore, convincing data are not available from the perspective of pharmacokinetics to support the fact that a dosage of 20 mg/kg of amikacin is sufficient to treat patients with ventilator-associated pneumonia (VAP). METHOD: This was a pilot study of amikacin concentration measurement in the alveolar site of action in critically ill adult patients with VAP who required aminoglycoside therapy. A dose of 20 mg/kg of amikacin was administered over a 30-minute infusion. The serum concentrations of amikacin were evaluated in the first, second, fourth, and sixth hours. However, the ELF concentration of amikacin was evaluated in the second hour with the help of bronchoalveolar lavage sampling technique. RESULTS: A total number of 8 patients was included in the study. The mean (SD) administered dose was 20 (0.9) mg/kg. The mean (SD) peak plasma concentration of amikacin was 59.6 (23) mg/L, with the volume of distribution of 0.36 (0.13)L/kg. The amikacin concentration in ELF was successfully measured in 7 patients (6.3) mg/L. The lung tissue penetration of the drug was described as alveolar percentage, proportional to both the first- and second-hour plasma concentrations, with a mean (SD) of 10.1% (8.4%) and 18% (16.7%), respectively. CONCLUSION: To our knowledge, the current study is the first that investigates whether standard doses of amikacin may lead to sufficient alveolar concentration of the drug. The results show that administration of amikacin in doses of 20 mg/kg in critically ill patients with VAP may not provide sufficient concentrations in ELF.
Authors: Aaron J Heffernan; Fekade B Sime; Derek S Sarovich; Michael Neely; Yarmarly Guerra-Valero; Saiyuri Naicker; Kyra Cottrell; Patrick Harris; Katherine T Andrews; David Ellwood; Steven C Wallis; Jeffrey Lipman; Keith Grimwood; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2020-08-20 Impact factor: 5.191
Authors: Aaron J Heffernan; Fekade B Sime; Sazlyna Mohd Sazlly Lim; Saiyuri Naicker; Katherine T Andrews; David Ellwood; Jeffrey Lipman; Keith Grimwood; Jason A Roberts Journal: Drugs R D Date: 2021-04-02
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