Fourfold increase in efficiency of cyclosporin A when combined with hyaluronan:Evidence for mode of drug transport and targeting
Gowland G
Prof. G. Gowland, Department of Experimental Pathology, The Medical College, Saint Bartholomew's Hospital, Charterhouse Square, London EC1M 6BQ
, United Kingdom
International Journal of Immunotherapy ( INT. J. IMMUNOTHER. )
(Switzerland)
, 1998
, 14/1 (1-7)
Language: ENGLISH
Summary Language: ENGLISH
Abstract: Cyclosporin A has potential for wide clinical use limited only by a very narrowtherapeutic index. Potentiation of its clinical efficacy is thus very desirable. Preliminary data had indicated that the admixture of cyclosporin A with hyaluronan could increase its efficacy. In this study it was found that the i.v. dose of cyclosporin A which inhibited oxazalone hypersensitivity in rats was reduced fourfold by the inclusion of cyclosporin A in hyaluronan. Cyclosporin A deliveryto draining lymph nodes increased correspondingly in the presence of hyaluronan. The availability of cyclosporin A to sensitized ears was reduced in direct relation to the efficacy of the formulation. An association of cyclosporin A with hyaluronan was demonstrated using gel filtration and shown to protect the cyclosporin A molecule from its normal predisposition to bind to red blood cells. A fourfold reduction in the dose of cyclosporin A required to inhibit T-cell functionin the whole organism has significant implication for its use in clinics, and would allow its more widespread use in chronic inflammatory disease, as well as reduced risk in the prevention of rejection in transplantation. (13 References)
Brands/Manufacturers: sandimmun sandoz Switzerland
sandoz Switzerlandhyal Canada
Subjects: - cyclosporin a --drug combination
- cyclosporin a --drug dose
- cyclosporin a --drug therapy
- cyclosporin a --pharmacokinetics
- hyaluronic acid --drug combination
- hyaluronic acid --drug therapy
- hyaluronic acid --pharmacokinetics
- oxazolone
- immunosuppressive agent --clinical trial
- immunosuppressive agent --drug administration
- immunosuppressive agent --drug combination
- immunosuppressive agent --drug dose
- immunosuppressive agent --drug therapy
- immunosuppressive agent
--pharmacokinetics
- drug transport
- drug targeting
- drug efficacy
- hypersensitivity --drug therapy
- lymph node
- gel filtration
- nonhuman
- male
- rat
- animal experiment
- controlled study
- animal tissue
- intravenous drug administration
- article
CAS® Registry Numbers: - 59865-13-3, 63798-73-2 (cyclosporin a)
- 31799-91-4, 9004-61-9, 9067-32-7 (hyaluronic acid)
EMBASE® (Excerpta Medica)
© 2001 Elsevier Science B.V. All rights reserved.
Dialog® File Number 73 Accession Number 7354779
|
