Serum Concentrations Of Itraconazole Research Articles

Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?

In regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success. Evaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA. The measurement was performed at least 7-days after initiation of therapy. The standard treatment at our institution was a 200mg capsule every 12h. We defined that an adequate serum trough concentration of itraconazole during treatment was 1-4mg/L. This study recruited 28 patients. The median value was 0.30mg/L (IQR 0.01-0.70). Only 11% (n = 3) had adequate serum concentrations based on guideline recommendation. All patients with clinical deterioration had itraconazole serum levels ≤ 0.8mg/L. The initial serum concentrations of itraconazole after capsule formulation administration were low. Increasing the dose should be considered when the itraconazole concentration is low, especially if it is ≤ 0.8mg/L, and the patient presents with clinical deterioration. Larger studies are needed to evaluate the adequate concentrations recommended for CPA.

Alternate-day dosing of itraconazole in healthy adult cats.

The current available formulations of itraconazole are not ideal for dosing in cats. The capsular preparation often does not allow for accurate dosing, the oral solution is difficult to administer and poorly tolerated, and the bioavailability of compounded formulations has been shown to be poor in other species. The aim of this study was to evaluate every other day dosing of 100 mg itraconazole capsule in healthy adult cats. Ten healthy adult cats received a 100 mg capsule of itraconazole orally every 48 h for 8 weeks. Peak and trough serum concentrations of itraconazole were measured weekly using high-performance liquid chromatography (HPLC). Physical examination, complete blood count (CBC), and chemistry profiles were performed weekly. The dosage regimen achieved average therapeutic trough concentrations (>0.5 μg/mL) within 3 weeks. The protocol yielded no adverse effects in 8 of the 10 study cats, with affected cats recovering fully with discontinuation of the drug and supportive care. At 8 weeks, an average peak concentration of 1.79 ± 0.952 μg/mL (95% CI: 0.996-2.588) and an average trough concentration of 0.761 ± 0.540 μg/mL (95% CI: 0.314-1.216) were achieved. Overall, a 100 mg every other day oral dosage regimen for itraconazole in cats yielded serum concentrations with minimal fluctuation and with careful monitoring may be considered for treatment of cats with systemic fungal disease.

A model for treating avian aspergillosis: serum and lung tissue kinetics for Japanese quail (Coturnix japonica) following single and multiple aerosol exposures of a nanoparticulate itraconazole suspension

Aspergillosis is frequently reported in parrots, falcons and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but administration requires repeated oral dosing and the safety margin is narrow. We describe lung tissue and serum pharmacokinetics of a nanoparticulate ITRA suspension administered to Japanese quail by aerosol exposure. Aerosolized ITRA (1 and 10% suspension) administered over 30 min did not induce adverse clinical reactions in quail upon single or 5-day repeated doses. High lung concentrations, well above the inhibitory levels for A. fumigatus, of 4.14 ± 0.19 μg/g and 27.5 ± 4.58 μg/g (mean ± SEM, n = 3), were achieved following single-dose inhalation of 1% and 10% suspension, respectively. Upon multiple dose administration of 10% suspension, mean lung concentrations reached 104.9 ± 10.1 μg/g. Drug clearance from the lungs was slow with terminal half-lives of 19.7 h and 35.8 h following inhalation of 1% and 10% suspension, respectively. Data suggest that lung clearance is solubility driven. Lung concentrations of hydroxy-itraconazole reached 1-2% of the ITRA lung tissue concentration indicating metabolism in lung tissue. Steady, but low, serum concentrations of ITRA could be measured after multiple dose administration, reaching less than 0.1% of the lung tissue concentration. This formulation may represent a novel, easy to administer treatment modality for fungal lung infection, preventing high systemic exposure. It may also be useful as metaphylaxis to prevent the outbreak of aspergillosis in colonized animals.

Endemic Fungal Infections in Solid Organ Transplant Recipients

Endemic Fungal Infections in Solid Organ Transplant Recipients

Antifungal serum concentration monitoring: an update

Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole).

Lnteracciones medicamentosas en pacientes bajo tratamiento con itraconazol para diferentes tipos de micosis

Some studies have reported an increasing number of clinically significant interactions of itraconazole in patients receiving drugs known to have profound effects on the cytochrome P-450 enzyme system. With the purpose of determining the epidemiological, pharmacological and clinical characteristics of drug interactions in patients under therapy with itraconazole, twenty-one patients with clinical and laboratory information suspicious of interaction were included in this transversal retrospective study undertaken during the period of 199441997, Six patients presented paracoccidioidomycosis, five chromoblastomycosis, four histoplasmosis, four cryptococcosis and two aspergillosis. Most of patients had either an underlying or concurrent illness like AlDS or tuberculosis. The average dose of itraconazole was 223.8 mglday, the mean duration of therapy was 23.1 weeks and each patients received around 2.6 drugs simultaneously administered with itraconazole. Drug interaction (undetectable or non-therapeutic serum concentrations of itraconazole) was found in 18 patients and rifampin, H, blockers, antiacids and phenytoin were the most common drugs implicated. According to some published articles, the concurrent administration of these drugs and itraconazole disturbed the absorption and metabolism of this antifungal, subsequently decreased its serum concentration and provoked therapeutic failure. This study is an initial approach that will allow to establish clues for the management of patient under therapy with itraconazole and other therapies and at risk of developing drug interactions.

Discrepancies associated with the measurement of itraconazole serum concentrations by bioassays

Discrepancies associated with the measurement of itraconazole serum concentrations by bioassays

Itraconazole solution: higher serum drug concentrations and better clinical response rates than the capsule formulation in acquired immunodeficiency syndrome patients with candidosis.

AIMS: To compare the serum concentrations of itraconazole and hydroxyitraconazole after treatment with itraconazole cyclodextrin solution and itraconazole capsules in human immunodeficiency virus (HIV) positive patients with oral candidosis. METHODS:...

Itraconazole suspension in the treatment of HIV-infected patients with fluconazole-resistant oropharyngeal candidiasis and esophagitis

Forty AIDS patients suffering from fluconazole-resistant oropharyngeal candidosis were treated with oral itraconazole solution (200-800 mg/day). In 39/49 patients the disease could be initially cured or significantly improved. In contrast to the good clinical results, however, only in six patients a yeast count reduction was observed, and in four patients unchanged high yeast counts persisted. The main pathogen was C. albicans. Even in longtime treatment itraconazole solution was well tolerated. In two patients only the therapy had to be stopped due to the increase of transaminases. Considerable individual deviations in serum concentrations of itraconazole or hydroxy-itraconazole, respectively, were observed which correlated only to a minor degree with clinical and mycological results. Application of itraconazole in a soluble preparation caused an increase in efficacy due to simultaneous local and systemic action. In the case of resistance to fluconazole the itraconazole solution is a valuable alternative to the administration of amphotericin B which is rich in adverse reactions.

Low Itraconazole Serum Concentrations Following Administration of Itraconazole Suspension to Critically Ill Allogeneic Bone Marrow Transplant Recipients

To report itraconazole serum concentrations following administration of itraconazole suspension via orogastric feeding tubes to 2 critically ill allogeneic bone marrow transplant recipients. A 38-year-old man and a 29-year-old man, each allogeneic bone marrow transplant recipients, were treated with oral itraconazole for documented fungal infections. Intubation and mechanical ventilation impeded ingestion of itraconazole capsules. Itraconazole was prepared initially as a suspension in intravenous lipid emulsion 20% and later as a suspension in citric acid 1.5% in D5W USP. Itraconazole serum concentrations were assayed using HPLC. Predose itraconazole serum concentrations were undetectable to 72 ng/mL. Postdose itraconazole serum concentrations were 5-97 ng/mL. Itraconazole concentrations measured in these patients were markedly lower than serum concentrations reported in the literature for similar doses administered to fed subjects. Efficacy of this antifungal agent is limited currently by the patient's ability to ingest and absorb the itraconazole capsules. Pathophysiologic factors and suspension formulation issues that likely contributed to decreased itraconazole absorption are discussed. Preparation and administration of itraconazole as a suspension did not enhance drug absorption in these patients. Furthermore, efficacy of itraconazole suspension may be affected by physical compatibility and chemical stability of the extemporaneous preparations.

Itraconazole-Didanosine Excipient Interaction

To the Editor. —Itraconazole, recently approved for the treatment of blastomycosis and histoplasmosis (Sporanox, Janssen Pharmaceutica, Piscataway, NJ), is a triazole antifungal with important activity against other fungal pathogens, including Candida albicans and Cryptococcus neoformans . 1 Reports of significant drug interactions with concurrent itraconazole therapy include increased cyclosporine and digoxin concentrations and reduced itraconazole serum concentrations when administered with rifampin, phenytoin, antacids, and histamine-2 antagonists. 1-3 We report a case suggestive of reduced itraconazole absorption when taken with didanosine. Report of a Case. —In October 1992, a 35-year-old Hispanic man presented to our clinic with primary complaints of headache, nausea, and vomiting for approximately 2 weeks. The patient's medical history was significant for the acquired immunodeficiency syndrome and cryptococcal meningitis. On successful completion of primary therapy for cryptococcal meningitis in May 1992 (cerebrospinal fluid lecithin cholesterol acyltransferase, 1:20), he was enrolled in a blinded evaluation of either fluconazole (400 mg/d)

Treatment of invasive aspergillosis with itraconazole

PURPOSE: Invasive aspergillosis in the immuno-compromised host is one of the most difficult therapeutic problems. Itraconazole, a new oral triazole, is inhibitory as well as fungicidal against Aspergillus species in vitro. It is active against Aspergillus infections in animal models. We present our experience with itraconazole therapy of 21 patients with aspergillosis. PATIENTS AND METHODS: Eeghteen of the 21 patients received 400 mg of itraconazole orally per day; the other three receiived 100 to 200 mg daily. Serum concentrations of itraconazole were measured and susceptibility testing was performed according to previously described methods. RESULTS: Of 15 evaluable patients, responses were produced in 12. Four of five with invasive pulmonary disease, two of two with skeletal disease, one of two with pleural disease, one of one with pericardial, sinus, mastoid, or hepatosplenic aspergillosis, and one of one with onychomycosis responded. One patient with carotid artery disease did not show a response, although results of cultures were negative at autopsy. One responder with joint disease had a possible relapse three months after completing 12 months of therapy. Ten of these patients were immunocompromised (including four with neutropenia and two renal transplant recipients) and eight of these responded. Side effects with itraconazole, in contrast to previously available therapy, were rare. CONCLUSION: This experience suggests itraconazole may be an important advance in the therapy of aspergillosis.