romurtide and Thrombocytopenia

N2-[(N-Acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a derivative of muramyl dipeptide (MDP), is known to promote recovery of peripheral leukocyte and platelet counts by inducing cytokines, especially colony stimulating factor (CSF) in myelosuppression secondary to anticancer therapy. This paper reviews the results of a double-blind comparative study on lung cancer patients, administered either 200 micrograms or 20 micrograms of muroctasin for 6 days post-chemotherapy. It demonstrates the efficacy of muroctasin, at 200 micrograms doses levels only, in promoting early recovery of leukocyte and platelet counts and hence the potential for earlier initiation of chemotherapy cycles. The most common side effect encountered during the study was transient fever.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Antineoplastic Agents; Biological Factors; Cytokines; Double-Blind Method; Humans; Leukopenia; Lung Neoplasms; Neutrophils; Platelet Count; Randomized Controlled Trials as Topic; Thrombocytopenia

We investigated the therapeutic effects of romurtide, a synthetic muramyl dipeptide derivative, on experimental thrombocytopenia induced by carboplatin in cynomolgus monkeys. A prolonged thrombocytopenia due to a severe myelosuppression was induced by carboplatin. Romurtide given subcutaneously elevated significantly the peripheral platelet counts during both early initiation and later recovery phase of thrombocytopenia, thereby shortening the time required for recovery to a normal platelet level and the duration of thrombocytopenia. An oral administration of romurtide was also found to have a similar therapeutic efficacy to subcutaneous administration. These results demonstrated a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Administration, Oral; Animals; Blood Platelets; Carboplatin; Cell Division; Disease Models, Animal; Female; Macaca fascicularis; Thrombocytopenia

The response of megakaryocytes and platelets to the administration of romurtide, a synthetic muramyl dipeptide derivative, was investigated in normal and irradiated guinea pigs. Romurtide was administered subcutaneously in a single dose or daily doses at levels of 1 to 100 micrograms/animal/day to normal animals to assess the dose response. Subsequently, dosage at 100 micrograms/animal/d for 8 consecutive days was initiated in separate groups of animals immediately after 1 Gy total body x-irradiation. In normal animals, a significant dose-dependent increase in the platelet count was noted, and a prolonged thrombocytopoiesis was detectable from 7 through 15 days after the initiation of romurtide administered for 8 days at a dose of 100 micrograms/animal/d. A significant increase in the white blood cell (WBC) count was also observed during days 1 through 11 after beginning romurtide treatment. In the irradiated animals, the treatment with romurtide increased platelet counts during the recovery phase of thrombocytopenia, thus apparently decreasing the time required for recovery to a normal platelet level. Before the rapid recovery of platelet counts by romurtide treatment, a marked increase in the number of megakaryocytes was noted as early as 7 days after irradiation. This increase was accompanied by an accelerated shift of the size distribution of megakaryocytes toward larger size class. Thus, the mean megakaryocyte size was significantly greater in guinea pigs receiving romurtide than in controls. Preceding the increase in the number of megakaryocytes, the serum interleukin-6 levels were found to be approximately 5 times greater than those in control animals. Treatment with romurtide diminished the WBC count nadir, resulting in significantly higher WBC count levels than in controls. Elevation of the plasma fibrinogen level was observed in the treated animals, and normalized gradually after discontinuation of romurtide treatment. These results indicate a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Blood Platelets; Bone Marrow Cells; Female; Fibrinogen; Guinea Pigs; Hematopoiesis; Interleukin-6; Leukocyte Count; Megakaryocytes; Platelet Count; Thrombocytopenia; Whole-Body Irradiation