![]() ![]() Lung delivery requires a particle size in the range of 1–5 μm ( 13, 15). In some instances, low or nondetectable plasma concentrations may be desirable in order to avoid systemic drug toxicities from prophylactic regimens or in patients with localized infections. Drugs delivered by the pulmonary route may or may not help treat systemic infection depending on the capacity to achieve adequate plasma concentration for therapy by this route of administration. The quantity of drug delivered may exceed attainable pulmonary concentrations when the drug is administered systemically. The wisdom regarding aerosol delivery of antimicrobials lies in the potential to deliver high concentrations of drug that exceed the inhibitory concentrations for target pathogens directly to the site of initial colonization and subsequent infection, the lung. Aerosol delivery of drugs can achieve greater local concentrations in the lung, which is frequently the site by which many pathogens gain entry into the body. In contrast to pMDIs and DPIs which administrate bolus doses of drugs, nebulizers deliver drugs in a continuous manner. Large quantities of drug can be administrated in this manner compared to pMDIs and DPIs. Nebulizers are used to administer drugs in the form of a liquid mist to the airways. Delivery devices include propellant-driven metered dose inhalers (pMDIs), dry powder inhalers (DPIs), and nebulizers ( 15). The drug utilizes biliary excretion as its primary route of elimination and is, therefore, not a concern when used in patients with renal dysfunction ( 2).Īerosol delivery of drugs has been widely adopted especially in asthma therapy and has been studied for many agents including corticosteroids, bronchodilators, antibiotics, and antifungal agents ( 13, 14). Micafungin is widely distributed into various tissue including liver, kidney, and lung tissues as demonstrated in rat and rabbit models ( 11, 12). Pharmacokinetic studies of micafungin suggest a linear dose-dependent relationship ( 9) in both pediatric and adult patients with a half-life of 14.6 ± 3 h ( 10). Due to large molecular weight and poor oral bioavailability, micafungin can only be administered intravenously. but is fungicidal against Candida spp., which may be explained by the difference in the relative abundance of 1,3-β- d-glucan in the fungal cell wall of the fungi ( 6– 8). ![]() Micafungin exhibits fungistatic activity against Aspergillus spp. 1,3-β- d-Glucan is essential for osmotic stability and integrity of the cell wall of several common fungal pathogens ( 4, 5). Micafungin acts as a noncompetitive inhibitor of the enzyme, 1,3-β- d-glucan synthase, an enzyme unique to fungi which is necessary for synthesis of 1,3-β- d-glucan. Micafungin was synthesized from a natural product of the fungus Coleophama empedri by certain modifications to improve its potency ( 3). The drug has been proven effective for prophylaxis against candidal infections in patients undergoing hematopoietic stem cell transplantation and for the treatment of esophageal candidiasis and invasive candidiasis ( 2). Micafungin sodium is an echinocandin antifungal agent ( 1) that was approved by the United States Food and Drug Administration in March 2005. Multivariate data analysis showed that this could be explained systematically by greater drug deposition on stages with larger cutoff sizes and reduced drug deposition on stages with smaller cutoff sizes rather than multimodal deposition or other anomalies in size distribution. These changes in MMAD were statistically significant by paired t test. The mass median aerodynamic diameter (MMAD) increased from 1.67 ± 0.05 to 1.77 ± 0.04 μm (Acorn II nebulizer) and from 2.09 ± 0.01 to 2.20 ± 0.01 μm (Pari LC Plus nebulizer) from the first to the second sampling periods. For the LC Plus nebulizer, FPF 5.8 was 92.3 ± 0.1 and FPF 3.3 was 67.0 ± 0.7 during the first sampling period. The Acorn II nebulizer delivered a fine particle fraction FPF 5.8 (%<5.8 μm) of 92.5 ± 0.8 and FPF 3.3 (%<3.3 μm) of 82.3 ± 2.1 during the first sampling period. The concentration of micafungin sodium increased by 21% when delivered by the Acorn II nebulizer and by 20% when delivered by the LC Plus nebulizer, respectively, from the first to the second sampling period. In the present pilot study, we characterize the performance of two nebulizers and their potential for delivering micafungin to the lungs as well as the use of multivariate data analysis for mass distribution profile comparison. Pulmonary delivery of micafungin has not previously been reported. Micafungin (Astellas Pharma US, Deerfield, IL, USA) has been shown to be an effective antifungal agent when administrated intravenously. Pharmaceutical aerosols have been targeted to the lungs for the treatment of asthma and pulmonary infectious diseases successfully.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |