mercaptopurine and Uremia

mercaptopurine has been researched along with Uremia* in 8 studies

Other Studies

8 other study(ies) available for mercaptopurine and Uremia

ArticleYear
Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China).
    Clinica chimica acta; international journal of clinical chemistry, 2007, Volume: 376, Issue:1-2

    Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. We determined a cut-off concentration of the TPMT activity assay less than which genotyping of the TPMT gene should be performed. In addition, the influence of hemodialysis on TPMT activity in uremic patients was examined.. In 248 healthy subjects and 30 uremic patients, PCR-based methods were used to analyze the most common functional mutations TPMT2, 3A, 3B and 3C. A HPLC assay was used to measure erythrocyte TPMT activity in the whole population.. Seven TPMT3C heterozygotes were identified, while TPMT2, 3A and 3B alleles were not detected in 248 healthy subjects. The frequency of TPMT3C allele was 1.4% (7/496). The TPMT activity in healthy subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with a mean of 16.03 +/- 4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%), and no TPMT deficiency subject was found. All of the 229 healthy subjects with high activity had no mutant alleles, while 7 of the 19 subjects with intermediate activity had a mutant allele. Phenotypes were in good agreement with genotypes for 95% of subjects. The uremic patients were all homozygous for the wild-type allele whose TPMT activity was activated significantly before hemodialysis compared with TPMT activity after hemodialysis.. We defined the cut-off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than which additional genotyping elucidates the individual risk for drug therapy. In uremic patients, TPMT activity is increased by some uremic factors, and dialysis shifted their TPMT activity close to that of a healthy control group.

    Topics: Adult; Asian People; China; Female; Gene Frequency; Genetic Testing; Genotype; Humans; Inactivation, Metabolic; Male; Mercaptopurine; Methyltransferases; Middle Aged; Phenotype; Polymorphism, Genetic; Renal Dialysis; Uremia

2007
Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain.
    Journal of neurochemistry, 2002, Volume: 83, Issue:1

    Renal impairment is associated with CNS dysfunctions and the accumulation of uremic toxins, such as indoxyl sulfate, in blood. To evaluate the relevance of indoxyl sulfate to CNS dysfunctions, we investigated the brain-to-blood transport of indoxyl sulfate at the blood-brain barrier (BBB) using the Brain Efflux Index method. [(3)H]Indoxyl sulfate undergoes efflux transport with an efflux transport rate of 1.08 x 10(-2)/min, and the process is saturable with a Km of 298 microm. This process is inhibited by para-aminohippuric acid, probenecid, benzylpenicillin, cimetidine and uremic toxinins, such as hippuric acid and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid. RT-PCR revealed that an OAT3 mRNA is expressed in conditionally immortalized rat brain capillary endothelial cell lines and rat brain capillary fraction. Xenopus oocytes expressing OAT3 were found to exhibit [(3)H]indoxyl sulfate uptake, which was significantly inhibited by neurotransmitter metabolites, such as homovanillic acid and 3-methoxy-4-hydroxymandelic acid, and by acyclovir, cefazolin, baclofen, 6-mercaptopurine, benzoic acid, and ketoprofen. These results suggest that OAT3 mediates the brain-to-blood transport of indoxyl sulfate, and is also involved in the efflux transport of neurotransmitter metabolites and drugs. Therefore, inhibition of the brain-to-blood transport involving OAT3 would occur in uremia and lead to the accumulation of neurotransmitter metabolites and drugs in the brain.

    Topics: Animals; Antimetabolites; Biological Transport; Blood-Brain Barrier; Brain; Capillaries; Cells, Cultured; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Endothelium, Vascular; GABA Agonists; Homovanillic Acid; Indican; Male; Microinjections; Neurotransmitter Agents; Oocytes; Organic Anion Transporters, Sodium-Independent; p-Aminohippuric Acid; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Uremia; Xenopus laevis

2002
Inhibition of PHA induced mononuclear cell proliferation by FK506 in combination with cyclosporine, methylprednisolone, 6-mercaptopurine and mycophenolic acid.
    Transplant immunology, 1993, Volume: 1, Issue:1

    In vitro inhibition of human peripheral blood mononuclear cell (PBMC) proliferation by immunosuppressive drugs has been shown to correlate with clinical outcomes in kidney transplant patients. The aim of our study was to analyse the degree of variability of in vitro interactions of FK506 (FK) with combinations of cyclosporin A (CyA), methylprednisolone (MP), 6-mercaptopurine (6ME), and mycophenolic acid (MPA) using phytohaemagglutinin (PHA) stimulated PBMCs. Our hypotheses were: that a wide range of interindividual variation would be detected; and that certain combinations of drugs would have a synergistic inhibitory effect on PHA stimulated PBMCs. Cells were cultured in supplemented RPMI 1640 for 65 hours at 37 degrees C in humidified 5% CO2 - 95% air and proliferative responses measured by 3H-thymidine incorporation over a further 24 hours. Inhibition of PBMC proliferation was assessed over 10 FK concentrations ranging from 1 x 10(-8) to 10 micrograms/ml using both volunteer controls (n = 51) and dialysis patients (n = 23). A wide range of interindividual variability of FK inhibition occurred throughout the range of FK concentrations tested, becoming less variable at the higher concentrations. The interactions of FK with CyA, MP, 6ME and MPA were assessed using PBMCs from 12 volunteer controls. For FK at 1 x 10(-8) micrograms/ml; CyA, MP, 6ME and MPA were used at 0.01 microgram/ml. For FK at 1 x 10(-7) micrograms/ml; CyA, MP, 6ME and MPA were used at 0.1 microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Cyclosporine; Drug Synergism; Humans; In Vitro Techniques; Kidney Transplantation; Lymphocyte Activation; Mercaptopurine; Methylprednisolone; Mycophenolic Acid; Phytohemagglutinins; Tacrolimus; Uremia

1993
Serum azathioprine and 6-mercaptopurine levels and immunosuppressive activity after azathioprine in uremic patients.
    International journal of immunopharmacology, 1986, Volume: 8, Issue:1

    The pharmacokinetics of azathioprine (AZA) and 6-mercaptopurine (6-MP) was studied in uremic patients after 100 mg AZA intravenously (fifteen patients) and orally (eight patients). 6-MP was analysed with gas chromatography mass spectrometry following extractive alkylation. AZA was determined indirectly assuming quantitative conversion to 6-MP in whole blood. The plasma concentration of AZA fell rapidly after i.v. administration. The mean half-time of elimination for the first rapid phase (t1/2 alpha) was 6.1 min (S.D. +/- 4.1) and for the terminal phase (t1/2 beta) 50 min (+/- 31). The total plasma clearance (Cl) was 6.9 1./min (+/- 3.0). AZA was rapidly converted to 6-MP in vivo, and maximal plasma concentrations of 6-MP were found as early as 5 min after i.v. injection of AZA. The mean t1/2 alpha was 4.6 min (+/- 2.2), t1/2 beta 74 min (+/- 58) and Cl 8.0 1./min (+/- 5.8). The plasma levels of both AZA and 6-MP were either low or undetectable 4-6 h after dose. In erythrocytes AZA levels were low or undetectable indicating rapid conversion to 6-MP in these cells. 6-MP concentration - time curve in erythrocytes was similar to that in plasma, except for a somewhat slower terminal phase of elimination. Oral administration of AZA generated flat plasma curves for AZA and 6-MP. The area under the concentration - time curve (AUC) was considerably smaller than after i.v. administration, 18 and 41% for AZA and 6-MP, respectively. There seems to be little danger of accumulation of AZA/6-MP in uremia. We also studied inhibition of Leucoagglutin (LA) stimulated lymphocyte proliferation by patient plasma at different times in six of the patients following AZA i.v. Sera drawn at 5, 10 and 30 min significantly inhibited the LA-induced proliferation, with an estimated minimum effective concentration of 6-MP in the cultures of about 0.02-0.04 microM. This suggests the possibility of a therapeutic effect even of the low plasma levels of 6-MP obtained after AZA orally. The combined use of sensitive pharmacokinetic and immunological assays as described should be useful in studying the relationship between plasma levels of AZA/6-MP and their immunosuppressive effect and toxicity.

    Topics: Administration, Oral; Adult; Azathioprine; Erythrocytes; Female; Humans; Immune Tolerance; Injections, Intravenous; Lymphocyte Activation; Male; Mercaptopurine; Middle Aged; Uremia

1986
Pharmacokinetics of azathioprine and 6-mercaptopurine: methodological aspects and preliminary results in uremic patients.
    Scandinavian journal of urology and nephrology. Supplementum, 1981, Volume: 64

    Topics: Administration, Oral; Animals; Azathioprine; Dogs; Erythrocytes; Freezing; Half-Life; Humans; Kidney Transplantation; Kinetics; Mercaptopurine; Uremia

1981
Assay of azathioprine, 6-mercaptopurine and a novel thiopurine metabolite in human plasma.
    British journal of clinical pharmacology, 1979, Volume: 8, Issue:3

    1 A simple, specific assay for 6-mercaptopurine (6-MP) in human plasma with a sensitivity of 10 ng/ml (66 nmol/1) has been developed. 2 6-MP was extracted directly from plasma into toluene using a novel extraction procedure. This involves conversion of 6-MP into a phenyl mercury derivative by its reaction with phenyl mercuric acetate in alkaline plasma and extracting into toluene. Back-extraction of the toluene layer with 0.1N HCl regenerates 6-MP, which is then oxidised to purine-6-sulphonate and assayed fluorimetrically. 3 This assay has been modified to measure azathioprine and a new thiopurine metabolite in plasma. 4 In a kidney transplant patient given azathioprine, 50 mg i.v., conversion to 6-MP was rapid and the plasma half-life of 6-MP was 36 min. 5 These assays are suitable for studying the pharmacokinetics of azathioprine in patients with kidney transplants. The 6-MP assay should also prove useful for studying the pharmacokinetics of the drug in patients with leukaemia.

    Topics: Azathioprine; Chemical Phenomena; Chemistry; Humans; Hydrogen-Ion Concentration; Hydrolysis; Kidney Transplantation; Mercaptopurine; Purines; Transplantation, Homologous; Uremia

1979
Treatment of adult leukemia with L-asparaginase (NSC-109229).
    Cancer chemotherapy reports, 1971, Volume: 55, Issue:3

    Topics: Adolescent; Adult; Aged; Allopurinol; Anaphylaxis; Asparaginase; Blood Coagulation Disorders; Cytarabine; Daunorubicin; Drug Hypersensitivity; Female; Fever; Gastrointestinal Hemorrhage; Hallucinations; Humans; Hyperglycemia; Injections, Intravenous; Jaundice; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Liver; Male; Mercaptopurine; Methotrexate; Middle Aged; Oral Hemorrhage; Prednisone; Thioguanine; Uremia; Vincristine; Vomiting

1971
PROLONGED REMISSION OF MYELOMA WITH CYCLOPHOSPHAMIDE.
    Archives of internal medicine, 1964, Volume: 113

    Topics: Adrenal Cortex Hormones; Blood Protein Electrophoresis; Bone Marrow Examination; Cyclophosphamide; gamma-Globulins; Humans; Hypercalcemia; Mechlorethamine; Mercaptopurine; Multiple Myeloma; Prognosis; Radiotherapy; Stilbamidines; Toxicology; Uremia; Urethane

1964