Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis.

Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.

Pattern of response of megakaryocyte colony-stimulating activity in the serum of patients undergoing bone marrow transplantation.

Bone marrow transplantation has become an accepted form of therapy for several malignant, hematologic, and genetic disorders. Platelet recovery is delayed after bone marrow transplantation. To better understand the mechanisms involved in platelet recovery we studied 23 patients undergoing bone marrow transplantation for the presence of megakaryocyte colony-stimulating activity (Mk-CSA) in their serum. Shortly after beginning the pretransplant preparative regimen the Mk-CSA level in the serum of these patients increased. This increase was transient, and the level returned to baseline, to later increase again. The second increase in Mk-CSA level occurred during the second week after bone marrow transplantation at the time of hematopoietic recovery. Most patients who failed to engraft did not show a rise in Mk-CSA during the second week after transplantation. All patients showing engraftment had an Mk-CSA rise during the second week after transplantation. The difference between these two groups was highly significant (p = 0.0007). The biphasic response of Mk-CSA after bone marrow transplantation is similar to the response seen in a rat model after lethal irradiation. We postulate that the first elevation in Mk-CSA is due to tissue injury and nonspecific response whereas the second elevation of Mk-CSA is a physiologic response to marrow aplasia and associated with effective bone marrow engraftment.