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Prospective, observational study of voriconazole therapeutic drug monitoring among lung transplant recipients receiving prophylaxis: factors impacting levels of and associations between serum troughs, efficacy, and toxicity.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2012 May; Vol. 56 (5), pp. 2371-7. Date of Electronic Publication: 2012 Feb 13. - Publication Year :
- 2012
-
Abstract
- Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients (n = 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs (n = 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 μg/ml, respectively. The age of the patient directly correlated with initial troughs (P = 0.005). Patients that were ≥ 60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients, ≥ 2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were ≤ 1.5 μg/ml or >1.5 μg/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml (P = 0.07). Invasive fungal infections or colonization were more likely with troughs of ≤ 1.5 μg/ml (P = 0.01) and among patients with no trough of >1.5 μg/ml (P = 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (P = 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of >1.5 μg/ml. A cutoff for toxicity was not identified, but troughs of >4 μg/ml were rare. The data support a target range of >1.5 to 4 μg/ml.
- Subjects :
- Adult
Aged
Antifungal Agents blood
Antifungal Agents pharmacokinetics
Central Nervous System drug effects
Central Nervous System microbiology
Central Nervous System pathology
Chromatography, High Pressure Liquid
Cystic Fibrosis blood
Cystic Fibrosis drug therapy
Cystic Fibrosis microbiology
Cystic Fibrosis pathology
Female
Fungi physiology
Humans
Liver drug effects
Liver microbiology
Liver pathology
Lung drug effects
Lung microbiology
Lung pathology
Male
Middle Aged
Prospective Studies
Pulmonary Fibrosis blood
Pulmonary Fibrosis drug therapy
Pulmonary Fibrosis microbiology
Pulmonary Fibrosis pathology
Pyrimidines blood
Treatment Outcome
Triazoles blood
United States
Voriconazole
Drug Monitoring
Fungi drug effects
Lung Transplantation
Mycoses prevention & control
Pyrimidines pharmacokinetics
Triazoles pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 56
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 22330924
- Full Text :
- https://doi.org/10.1128/AAC.05219-11