mercaptopurine and pyrimidine

A survey is given of our present investigations of the pharmacokinetics of 6MP and the effects of the combination of MTX and 6MP on purine and pyrimidine metabolism. Both drugs are used in the oral maintenance therapy of ALL in children. The very low serum-concentrations after oral administration of 6MP and the short serum-half-life-times after intravenous administration point to more efficacy after prolonged intravenous infusion. The penetration of 6MP in the cerebrospinal fluid after intravenous administration could account for (prophylactic) treatment of the CNS in ALL. Pretreatment of leukemic lymphoblasts with MTX results in an increase of intracellular PRPP due to inhibition of purine de novo synthesis. This can be used for an increased incorporation and conversion of 6MP. Thus, increased incorporation and conversion of 6MP can be obtained when 6MP is added to MTX-pretreated leukemic lymphoblasts at that point of time where MTX causes maximal PRPP accumulation. This will result in increased incorporation of 6MP into nucleic acids and thus in enhanced cytotoxicity. Pharmacokinetic and metabolic investigations of 6MP and MTX could lead to a more rational and more effective use of both agents in patients with ALL.

Topics: Animals; Child; Dogs; Half-Life; Humans; Infusions, Parenteral; Leukemia, Lymphoid; Lymphocytes; Mercaptopurine; Methotrexate; Purines; Pyrimidines

Topics: Adenine; Caffeine; Carbon Isotopes; Guanine; Intestine, Small; Intestines; Mercaptopurine; Pharmacology; Physiology; Purines; Pyrimidines; Rats; Research; Theobromine; Theophylline; Uracil; Uric Acid; Xanthines

Topics: Animals; Antineoplastic Agents; Ascites; Azaserine; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Neoplasms, Experimental; Pyrimidines; Thioguanine

Topics: Animals; Ascites; Azaserine; Azoles; Carcinoma, Ehrlich Tumor; Humans; Mercaptopurine; Neoplasms; Neoplasms, Experimental; Pyrimidines; Serine; Thioguanine