FAURISSON F, DELATOUR F, DEQUIN PF, JELAZKO P, DIOT P; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 18.
INSERM EMI 9933, Paris, France
BACKGROUND: Aerosolized aminoglycosides have been proven effective in P. aeruginosa infection in cystic fibrosis (CF) and depends on properly deposed dose (DD). Depending on nebulization and inhalation, there is a wide variability in DD. As previously shown, 24 hour urinary amikacin excretion (AMK[u24]) correlates with DD. On the other hand it represents 85% of the systemic dose which may potentially result in toxicity. So AMK[u24] may be of interest both for efficacy and safety monitoring. We developped a tool of monitoring by estimation of AMK[u24], based on a single-sample urine assay.METHODS: Eighty-seven courses of 24 hour urine pharmacokinetics, in healthy volunteers ( HV: groups A and B) or in CF (groups C and D) were studied. Taking into account actual AMK[u24] (A AMK[u24]), the rules of determination of estimated AMK[u24] (E AMK[u24]), based on 6, 8, 10 or 12 hour urine samplings, were determined on A. Their accuracy were then tested B, C and D. Collection of a single sample for 8 to 12 hour periods requires an early morning sampling of overnight urine, thus circadian variation of creatininuria rate was studied in C.RESULTS: High variability in A AMK[u24] was found both in HV and CF as shown by their coefficients of variation (CV), 36%, 30%, 48% and 82% respectively for A, B, C and D. The accuracy of E AMK[u24] was evaluated by E AMK[u24]/A AMK[u24] ratio which ranged from 0.95 to 1.05 in B, C and D, showing the lack of bias in estimation. In addition CV of these ratios were only 10-15% in B and 4 to 8% in C and D, making possible an accurate individual estimation. Very low circadian changes in renal function (range: - 2% + 5%) demonstrated the lack of bias due to night sampling. Conclusion: A single-sample urine assay may be proposed as simple, non invasive, low cost and accurate method for clinical monitoring of aerosolized amikacin in CF.KEYWORDS: Amikacin; Cystic fibrosis; Drug monitoring
Publication Types:
Keywords:
- Amikacin
- Aminoglycosides
- Anti-Bacterial Agents
- Biological Assay
- Cystic Fibrosis
- Drug Monitoring
- Humans
- Monitoring, Physiologic
- Single Person
- analysis
- methods
- pharmacokinetics
- urine
Other ID:
UI: 102248593
From Meeting Abstracts