Author(s): Hirabayashi H, Takahashi T, Fujisaki J, Masunaga T, Sato S, et al.
We have newly synthesized osteotropic diclofenac with bisphosphonic moiety (DIC-BP) based on the concept of Osteotropic Drug Delivery System (ODDS) and investigated its potency of site-specific and controlled delivery of diclofenac to the bone in rats. After intravenous injection into rats, DIC-BP was predominantly distributed in the skeleton. DIC-BP once incorporated in the bone was gradually eliminated (t(1/2)=9.7 days), releasing diclofenac into the bone compartment. As a result, the bone concentration of regenerated diclofenac was apparently constant over 28 days. Furthermore, we evaluated the anti-inflammatory effects of DIC-BP compared with diclofenac (sodium salt) in adjuvant-induced arthritic rats. The mean effective doses (ED(50)) were 0.55 mg/kg and 1.3 mg/kg for daily oral administration of diclofenac and weekly intravenous injection of DIC-BP, respectively. Considering the frequency of medication of 17 times for diclofenac and 4 times for DIC-BP in the experimental period, ED(50) was corrected to 9.4 and 5.2 mg/kg (per experimental period) for diclofenac and DIC-BP, respectively. Moreover, DIC-BP exhibited no side effects of gastrointestinal damage, typical of non-steroidal anti-inflammatory drugs. Thus, ODDS of diclofenac shows promise as an approach for highly potent and non-toxic therapy of diclofenac, with less frequent medication.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/11166418
Author(s): McLeod AD, Fedorak RN, Friend DR, Tozer TN, Cui N
Author(s): McLeod AD, Friend DR, Tozer TN
Author(s): Fedorak RN, Haeberlin B, Empey LR, Cui N, Nolen H 3rd, et al.
Author(s): Fedorak RN, Cui N, Friend DR, Madsen KL, Empey LR
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Author(s): Kong L, Cooperwood JS, Oh CH, Chu CK, Boudinot FD
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Author(s): Friedrich RB, Ravanello A, Cichota LC, Rolim CMB, Beck RCR