In the lung aerosol cyclosporine provides a regional concentration advantage over intramuscular cyclosporine
| Autor: | Kenneth R. McCurry, Aldo Iacono, Surindra N. Mitruka, Teresa P. McKaveney, Bartley P. Griffith, Raman Venkataramanan, Gilbert J. Burckart, Alvina Won, Adriana Zeevi |
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| Rok vydání: | 2000 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty medicine.medical_treatment Urology Injections Intramuscular Dosage form Refractory Administration Inhalation Animals Medicine Tissue Distribution Lung Aerosols Transplantation Chemotherapy Inhalation business.industry respiratory system Ciclosporin Rats medicine.anatomical_structure Rats Inbred Lew Anesthesia Cyclosporine Surgery Cardiology and Cardiovascular Medicine business Complication Immunosuppressive Agents medicine.drug |
| Zdroj: | The Journal of Heart and Lung Transplantation. 19:969-975 |
| ISSN: | 1053-2498 |
| Popis: | Background: Acute rejection remains an almost universal complication among lung transplant recipients. Refractory rejection as well as chronic systemic immunosuppression is associated with significant morbidity and mortality. Recent studies suggest that aerosol cyclosporine may address these issues by effectively preventing acute cellular rejection while maintaining low systemic drug concentrations. This study was designed to evaluate the concentrations of cyclosporine in blood and lung tissue after aerosol and intramuscular administration. Methods Lewis rats were divided into 4 experimental groups: Groups A ( n = 33) and B ( n = 30) received aerosol cyclosporine 3 and 5 mg/kg, respectively; Groups C ( n = 33) and D ( n = 30) received systemic cyclosporine 5 and 15 mg/kg, respectively. We used high-performance liquid chromatography to quantitate blood and lung tissue cyclosporine levels at timed intervals. We used the trapezoidal rule to approximate area under the concentration vs time curve (AUC). Results Aerosol delivery of cyclosporine resulted in higher and more rapid peak drug levels in lung tissue samples than did systemic delivery. At an equivalent 5 mg/kg dose, the cyclosporine AUC was 3 times higher with aerosol delivery than with intramuscular delivery in lung tissue (477,965 vs 157,706 ng × hour/g, respectively). The lung tissue: blood AUC ratio was highest in the aerosol groups (27.3:1 and 17.4:1) compared with the intramuscular groups (8.1:1 and 9.4:1). Conclusion Local aerosol inhalation delivery of cyclosporine provides a regional advantage over systemic intramuscular therapy by providing higher peak concentrations and greater lung tissue exposure. |
| Databáze: | OpenAIRE |
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