Nucleic acids. 16. Orally active derivatives of ara-cytidine.

Water-soluble derivatives of ara-cytidine (cytarabine, Cytosar) were prepared and tested for antitumor, immunosuppressive, and antiarthritic activities in animals after oral administration. The compounds tested included the 5'-palmitate, 5'-benzoate, and 5'-adamantoate esters of ara-cytidine, made water soluble by use of their hydrochloride salts of peptidyl derivatives, and two basic 5' esters (5'-nicotinoate and 5'-quinuclidinate) as their hydrochloride salts. Five of the compounds had antitumor activity superior to that found with ara-cytidine itself after oral administration in the L1210 leukemic mouse assay. One of these, 5'-adamantoyl-ara-cytidine hydrochloride, had antitumor activity after oral administration approaching that achieved with parenterally administered ara-cytidine.

Ibuprofen versus buffered phenylbutazone in the treatment of osteoarthritis: double-blind trial.

In a double-blind multiclinic trial, a new nonsteroidal anti-inflammatory agent (ibuprofen) was compared with an established therapeutic agent (phenylbutazone-alka) for the treatment of osteoarthritis. Of the 159 patients from the 17 contributing clinics, 144 completed the four weeks of therapy. More than 60 per cent of them reported improvement in exercise-related pain by week 4, and there was no significant difference between treatment groups. The patients' and the physicians' evaluations of the total state of disease, as well as range-of-motion and functional tests, demonstrated similar degrees of improvement in both treatment groups. The incidence of side effects was within acceptable limits, and the frequency distribution was similar in both groups. Of the 70 reported side effects, 29 were considered by the investigator (blind trial) to be drug-related-11 in association with ibuprofen and 18 with phenylbutazone-alka. Hematologic and blood chemical studies, as well as urine and stool examinations, yielded normal results with the exception of a reduced mean value for serum uric acid and a slightly elevated mean value for SGPT in the phenylbutazone-alka group.

A long-term double-blind clinical trial of ibuprofen and indomethacin in rheumatoid arthritis.

Two-hundred and eighteen individuals with rheumatoid arthritis were randomly assigned to six months treatment with ibuprofen (900-1800 mg/day) or indomethacin (75-150 mg/day). The drugs were equally effective in the treatment of rheumatoid arthritis while the incidence of indomethacin side-effects was 1.5 times greater than the incidence of ibuprofen side-effects.

Enhancement by tetrahydrouridine (NSC-112907) of the oral activity of 5-azacytidine (NSC-102816) in L1210 leukemic mice.

5-Azacytidine is more active when administered parenterally than orally in the treatment of L1210 leukemic mice. Oral coadministration of tetrahydrouridine, a pyrimidine nucleoside deaminase inhibitor with no intrinsic antitumor activity, greatly increases the oral activity of 5-azacytidine. 5-azacytidine (or cytotoxic equivalent) blood levels in BDF mice are much higher after oral administration of the 5-azacytidine-tetrahydrouridine combination than when 5-azacytidine is administered alone by the same route. The therapeutic results (L1210 leukemia) achieved with the oral combination are similar to those observed with parenteral 5-azacytidine alone.