Low doses of dexamethasone constantly delivered by autologous erythrocytes slow the progression of lung disease in cystic fibrosis patients.
OBJECTIVE
To evaluate the safety and efficacy of the administration of low doses of glucocorticoids in patients with cystic fibrosis (CF) by using autologous erythrocytes loaded with dexamethasone 21-phosphate.


METHODS
Nine consecutive CF patients (patients nos. 1-9) received autologous erythrocytes loaded with increasing amounts of dexamethasone 21-phosphate to obtain a slow delivery of dexamethasone in circulation. The appearance of possible adverse effects, the reproducibility of the procedure, and the dexamethasone pharmacokinetics were evaluated. Subsequently, patient no. 9 and eight additional patients (patient nos. 10-17) received dexamethasone 21-phosphate-loaded erythrocytes at 1-month intervals to evaluate the efficacy of continuous release in circulation of low doses of dexamethasone.


RESULTS
Erythrocytes from CF patients can be processed to be loaded with increasing dexamethasone 21-P concentrations. Once reinfused in respective donors, a slow and prolonged delivery of dexamethasone in the blood stream was measured up to 28 days. Repeated administrations of drug-loaded erythrocytes at 4-week intervals for 15 months showed that very low doses of glucocorticoids provide significant improvement in FEV1 values and significant reduction of infective relapses due to Pseudomonas aeruginosa without adverse effects.


CONCLUSIONS
The administration of very low doses of glucocorticoids using autologous erythrocytes is possible, with benefits for patients and without side effects. This method is likely to be extended to other chronic diseases.
Rossi
Luigia
L
Institute of Biological Chemistry G. Fornaini, University of Urbino, 61029 Urbino, Italy.
Castro
Massimo
M
D'Orio
Francesco
F
Damonte
Gianluca
G
Serafini
Sonja
S
Bigi
Leonardo
L
Panzani
Ivo
I
Novelli
Giuseppe
G
Dallapiccola
Bruno
B
Panunzi
Simona
S
Di Carlo
Pierluigi
P
Bella
Sergio
S
Magnani
Mauro
M
D000293:Adolescent; D000328:Adult; D001804:Blood Transfusion, Autologous; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications / Q000628:therapy*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018450:Disease Progression; D017707:Erythrocyte Transfusion / Q000379:methods*; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*; D011552:Pseudomonas Infections / Q000209:etiology / Q000628:therapy; D011550:Pseudomonas aeruginosa; D055502:Secondary Prevention; D016896:Treatment Outcome
C004180:dexamethasone 21-phosphate; D003907:Dexamethasone