Interaction of indometacin farnesil, a new nonsteroidal antiinflammatory drug with peripheral blood mononuclear cells from patients with rheumatoid arthritis.

Abstract	Indometacin farnesil (Indo-F) is a prodrug of indomethacin designed to reduce the occurrence of side-effects by esterification of the carboxyl group on indomethacin with farnesol. We have examined the pharmacological kinetics and action of Indo-F in peripheral blood mononuclear cells (PBMNC) and polymorphonuclear leukocytes (PBPNL) from patients with rheumatoid arthritis (RA). PBMNC and PBPNL were obtained from 31 RA patients. Indo-F was incubated with PBMNC or PBPNL in the presence or absence of granulocyte-macrophage colony stimulating factor (GM-CSF) (100 pg/ml) for 3 approximately 7 days, after which the concentrations of Indo-F and indomethacin in the culture supernatants or in the cytoplasm extracts were measured with HPLC. The levels of Indo-F in the culture supernatants were significantly decreased in the presence of PBMNC or PBPNL from either normal individuals or RA patients. Indo-F was found to be taken up by PBMNC as well as by PBPNL from RA patients. Conversion of Indo-F into indomethacin was significantly enhanced by GMCSF in the presence of PBMNC, but not PBPNL. The results indicate that Indo-F is taken up by peripheral blood leukocytes from RA patients. Moreover, the data suggest that monocyte-lineage cells might play an important role in the conversion of Indo-F into indomethacin since GM-CSF markedly facilitated the conversion in the presence of PBMNC, but not PBPNL.
Authors	S Hirohata, K Konuma, T Inoue, K Ito
Journal	Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology (Nihon Rinsho Meneki Gakkai Kaishi) Vol. 19 Issue 2 Pg. 136-44 (Apr 1996) ISSN: 0911-4300 [Print] Japan
PMID	8705690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Inflammatory Agents, Non-Steroidal Prodrugs indomethacin farnesil Indomethacin
Topics	Adult Aged Anti-Inflammatory Agents, Non-Steroidal (therapeutic use) Arthritis, Rheumatoid (blood, drug therapy) Female Humans Indomethacin (analogs & derivatives, therapeutic use) Leukocytes, Mononuclear (drug effects) Male Middle Aged Neutrophils (drug effects) Prodrugs (therapeutic use)

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