Once-a-day oral dosing regimen of cyclosporin A: combined therapy of cyclosporin A premicroemulsion concentrates and enteric coated solid-state premicroemulsion concentrates.
OBJECTIVE
To develop once-a-day oral dosing regimen that provides the blood levels of cyclosporin A (CsA) in the therapeutic ranges over 24 hours.


METHODS
CsA premicroemulsion concentrates (preME) were formulated from phase diagrams. Enteric-coated solid-state premicroemulsion concentrates (sME) were prepared by coating preME with enteric-coating matrials and solidifying them. CsA was measured using high-performance liquid chromatography or radioimmunoassay.


RESULTS
PreME consisted of CsA, oil, and mixture of surfactants and a cosurfactant. PreME spontaneously formed microemulsions in aqueous medium and showed oral absorption profiles similar to Sandimmune Neoral in dogs. Dispersion of sME in aqueous medium also formed microemulsions. Release rates of CsA from sME depended on pH and the type of enteric-coating materials and highly correlated with the extent of oral absorption. The co-administration of preME and sME (200 mg CsA) showed the maximum blood level of CsA not significantly different from that of preME (100 mg CsA) and the concentration of CsA close to the minimum therapeutic level at 24 hours.


CONCLUSIONS
The combined treatment of preME and sME provided controlled oral absorption of CsA over a 24-hour period. Such once-a-day dosing regimens will lead to increased patient compliance and reduced episodes of organ rejection after transplantation.
Kim
C K
CK
College of Pharmacy, Seoul National University, South Korea. ckkim@plaza.snu.ac.kr
Shin
H J
HJ
Yang
S G
SG
Kim
J H
JH
Oh
Y K
YK
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood; D004285:Dogs; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004655:Emulsions; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D013608:Tablets, Enteric-Coated
D004655:Emulsions; D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine