THERAPEUTIC DRUG MONITORING OF AMIKACIN: METHODS AND RESULTS IN PATIENTS WITH CYSTIC FIBROSIS

Authors

  • Aleksandar Nikodinkvski Institute of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Stojka Fushtikj Naceva University Clinic for Pediatric Diseases, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Jasmina Pavlovska-Trojachanec Institute of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Krume Jakjovski Institute of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Bojan Labachevski Institute of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Nikola Kolovchevski Institute of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Marija Perkovikj Bujaroska Institute of Forensic Medicine, Criminology and Medical Deontology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Zorica Bozhinoska Institute of Forensic Medicine, Criminology and Medical Deontology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Grupche Dijana General Hospital Ohrid, Ohrid, Republic of North Macedonia
  • Nikola Labachevski Institute of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia

Keywords:

Amikacin, therapeutic drug monitoring, fluorescence polarization immunoassays, cystic fibrosis,safety

Abstract

Introduction: Therapeutic drug monitoring (TDM) is essential to optimize amikacin therapy, especially in patients with cystic fibrosis (CF), due to a small therapeutic index and significant interpatient variability. This study presents the methods and results of TDM in CF patients treated with amikacin.

Methods: A prospective, open-label clinical study was conducted in CF patients receiving amikacin. Amikacin serum concentrations were measured using a fluorescence polarization immunoassay (FPIA). Peak and trough concentrations were recorded to maintain therapeutic levels and minimize toxicity. Data on patients’ demographics, renal function, and clinical outcome were also collected.

Results: Amikacin serum concentrations were determined in a total of 165 blood samples taken from 33 patients who received amikacin at a dose of 30 mg/kg, but not more than 1.5 g, in the form of an intravenous infusion over 30 minutes once a day. Maximum concentrations of amikacin in patients ranged from 29.6-197.7 µg/ml, while minimum values ​​were always < 2 µg/ml in all patients in the study. No cases of nephrotoxicity and ototoxicity were observed.

Conclusion: According to literature, TDM of amikacin in CF patients is crucial to achieve optimal therapeutic results. Because no dose adjustment was required in any patient in our study, determination of amikacin concentrations in our population is justified only in patients with decreased therapeutic efficacy of the drug or in the case of adverse effects.

References

Kang JS, Lee MH. Overview of therapeutic drug monitoring. Korean J Intern Med 2009; 24(1): 1-10. doi: 10.3904/kjim.2009.24.1.1.

Ghiculescu RA. Therapeutic drug monitoring: which drugs, why, when and how to do it. Australian Prescriber 2008; 31(2): 42-44. ttps://doi.org/10.18773/austprescr.2008.025.

Jenkins A, Thomson AH, Brown NM, Semple Y, Sluman C, MacGowan A, et al. (BSAC Working Party on Therapeutic Drug Monitoring). Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review. J Antimicrob Chemother 2016; 71(10): 2754-2759. doi: 10.1093/jac/dkw250.

Craig WA. Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men. Clinical Infectious Diseases 1998; 26(1): 1-10. doi: 10.1086/516284.

Begg EJ, Barclay ML, Kirkpatrick CJ. The therapeutic monitoring of antimicrobial agents. British Journal of Clinical Pharmacology 1999; 47(1): 23-30. doi: 10.1046/j.1365-2125.1999.00850.x.

Lenoir M, Puel J. Dose dependent changes in the rat cochlea following aminoglycoside intoxication. II. Histological study. Hear Res 1987; 26(2): 199-209. doi: 10.1016/0378-5955(87)90112-2.

Rodvold AK. Pharmacodynamics od anti-infective therapy: Taking what we know to the patients bedside. Pharmacotherapy 2001; 21(11 Pt 2): 319S-330S. doi: 10.1592/phco.21.18.319s.33904.

Banerjee S, Narayanan M, Gould K. Monitoring aminoglycoside level. BMJ 2012; 345: e6354. https// doi.org/10.1136/bmj.e6354.

Avent ML, Rogers BA, Cheng AC, Paterson DL. Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity. Internal medicine J 2011; 41(6): 441-449. doi: 10.1111/j.1445-5994.2011.02452.x.

Kirby WMM, Perry DM, Bauer AW. Treatment of staphylococcal septicemia with vancomycin. N Engl J Med 1960; 262: 49-55. doi: 10.1056/NEJM196001142620201.

Gump DW. Vancomycin for treatment of bacterial meningitis. RevInfectDis 1981; 3: S289-292. PMID: 6896243.

Bailie GR, Neal D. Vancomycin ototoxicity and nephrotoxicity. A review. Med Toxicol Adverse Drug Esp 1988; 3(5): 376-386. doi: 10.1007/BF03259891.

Downloads

Published

2024-07-09

Issue

Vol. 4 No. 2 (2024): Acad Med J

Section

Original Articles