BACKGROUND: Prevalence of oral mucosal fungal infections increases with the frequent administration of antibiotics, corticosteroids and immunosuppressive drugs. Therapeutically used antifungals are usually associated with a variety of drug interactions. Furthermore, there has been a noticeable increase in microorganisms resistant to these preparations. Mucoadhesive buccal films represent a modern therapeutic system for the treatment of oral mucosal fungal infection paired with a high degree of patient compliance. Ciclopirox olamine applied directly onto the oral mucosa offers an attractive alternative to treatment with systemic antifungals thanks to its low incidence of resistance and side effects. OBJECTIVE: The aim of this work was to evaluate the pharmacokinetic parameters of ciclopirox olamine after the buccal application of mucoadhesive film prepared by the solvent casting method. METHOD: A chromatographic method using an internal standard was developed and validated for evaluation of ciclopirox olamine plasma concentrations. Method accuracy was 88.5-104.6% and 89.5-99.7% for interday and intraday assays, respectively. RESULTS: The pharmacokinetic properties of ciclopirox olamine were studied in New Zealand White rabbits. The mucoadhesive films containing ciclopirox olamine in a total dose of 34.4 (33.0; 35.9) mg kg-1 were applied to all the rabbits. Plasma ciclopirox olamine concentrations were determined during the 12 h following application. The time taken to reach maximum plasma concentration was 1.7 (1.1; 2.2) h after the drug administration with cmax 5.73 (4.18; 7.28) μg mL-1. Overall elimination half-life was 3.8 (1.9; 10.8) h. CONCLUSION: The experiment suggests that oral mucoadhesive film may be a valuable alternative ciclopirox olamine administration.
- MeSH
- antifungální látky aplikace a dávkování krev farmakokinetika MeSH
- aplikace bukální MeSH
- králíci MeSH
- molekulární struktura MeSH
- pyridony aplikace a dávkování krev farmakokinetika MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Voriconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of voriconazole TDM to guide therapy remains uncertain and controversial. We conducted a meta-analysis of studies assessing the relationship between voriconazole serum concentration and clinical outcomes of success and toxicity. METHODS: We searched bibliographic databases for studies on voriconazole serum concentrations and clinical outcomes. We compared success outcomes between patients with therapeutic and subtherapeutic voriconazole serum concentrations, and toxicity outcomes between patients with and without supratherapeutic serum concentrations. RESULTS: Twenty-four studies were analysed. Pooled analysis for efficacy endpoint demonstrated that patients with therapeutic voriconazole serum concentrations (1.0-2.2 mg/L) were more likely to have successful outcomes compared with those with subtherapeutic voriconazole serum concentrations (OR 2.30; 95% CI 1.39-3.81). A therapeutic threshold of 1.0 mg/L was most predictive of successful outcome (OR 1.94; 95% CI 1.04-3.62). Patients with therapeutic concentrations did not have better survival rates. Pooled analysis for toxicity endpoint demonstrated that patients with supratherapeutic voriconazole serum concentrations (4.0-6.0 mg/L) were at increased risk of toxicity (OR 4.17; 95% CI 2.08-8.36). A supratherapeutic threshold of 6.0 mg/L was most predictive of toxicity (OR 4.60; 95% CI 1.49-14.16). CONCLUSIONS: Patients with therapeutic voriconazole serum concentrations were twice as likely to achieve successful outcomes. The likelihood of toxicity associated with supratherapeutic voriconazole serum concentrations was 4-fold that of therapeutic concentrations. Our findings suggest that the use of voriconazole TDM to aim for serum concentrations between 1.0 and 6.0 mg/L during therapy may be warranted to optimize clinical success and minimize toxicity.
- MeSH
- antifungální látky škodlivé účinky krev terapeutické užití MeSH
- invazivní mykotické infekce farmakoterapie prevence a kontrola MeSH
- lidé MeSH
- monitorování léčiv * MeSH
- mykózy farmakoterapie MeSH
- vorikonazol škodlivé účinky krev terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- plazmatická koncentrace léčiva,
- MeSH
- analgetika MeSH
- antiastmatika farmakokinetika farmakologie krev škodlivé účinky MeSH
- antibakteriální látky farmakokinetika farmakologie krev MeSH
- antidepresiva farmakokinetika farmakologie krev MeSH
- antifungální látky farmakologie krev MeSH
- antikonvulziva farmakologie krev MeSH
- antipyretika MeSH
- cytostatické látky farmakologie krev MeSH
- farmakoterapie metody trendy MeSH
- hodnocení rizik MeSH
- imunosupresiva farmakologie krev škodlivé účinky MeSH
- individualizovaná medicína trendy MeSH
- kardiovaskulární látky farmakologie krev MeSH
- lidé MeSH
- monitorování léčiv * klasifikace metody statistika a číselné údaje trendy MeSH
- trankvilizéry farmakokinetika farmakologie krev MeSH
- Check Tag
- lidé MeSH
The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1-27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3% of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high-pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml(-1) (range <0.20-13.47 μg ml(-1)). Significant inter- and intra-patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice.
- MeSH
- antifungální látky aplikace a dávkování škodlivé účinky krev MeSH
- aromatické hydroxylasy genetika MeSH
- aspergilóza komplikace farmakoterapie genetika MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus MeSH
- krevní nemoci komplikace farmakoterapie genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- monitorování léčiv * MeSH
- pyrimidiny aplikace a dávkování škodlivé účinky krev MeSH
- retrospektivní studie MeSH
- senioři MeSH
- triazoly aplikace a dávkování škodlivé účinky krev MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antifungální látky aplikace a dávkování krev MeSH
- lidé MeSH
- monitorování léčiv MeSH
- neutropenie komplikace MeSH
- triazoly aplikace a dávkování krev MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Stanovení in vitro citlivosti mikromycet k antifungálním látkám nabývá na významu se vzrůstajícím výskytem mykotických infekcí a rozšiřující se paletou antifungálních preparátů. V posledních letech byly standardizovány metody vhodné k testování citlivosti kvasinek a vláknitých mikromycet k antimykotikům a došlo i k rozšíření nabídky komerčně dodávaných souprav pro stanovení citlivosti odvozených od těchto standardů. V článku je uváděn přehled standardizovaných mikrodilučních kvantitativních metod, metodika diskových difúzních testů a hodnocení komerčně dostupných testů vhodných pro rutinní použití v mykologických laboratořích. Pro vysokou korelaci se standardy CLSI je doporučován Etest, jehož propracovaná metodika včetně interpretace zaručují kvalitní a vzájemně reprodukovatelné výsledky. Pro posouzení farmakokinetiky je doporučováno stanovení hladin antimykotik v séru pacienta.
With the rising incidence of fungal infections and a widening range of antifungal agents, determining the in vitro susceptibility of microfungi to antifungals is increasingly important. Recent years have seen standardization of methods suitable for testing the susceptibility of yeasts and filamentous fungi to antifungals and a wider choice of commercially supplied kits for determining susceptibility derived from those standards. The texts surveys standard microdilution quantitative methods, disk diffusion tests and assessment of commercially available tests suitable for routine use in mycology laboratories. The Etest is recommended for its high correlation with the CLSl standards and sophisticated methodology including interpretation, which guarantees high quality and reproducible results. To assess pharmacokinetics, determination of antifungal levels in the patient's serum is recommended.
