Effect of mycophenolate mofetil therapy on inosine monophosphate dehydrogenase induction in red blood cells of heart transplant recipients.
Clin Pharmacol Ther
; 69(3): 137-44, 2001 Mar.
Article
em En
| MEDLINE
| ID: mdl-11240978
ABSTRACT
BACKGROUND:
Mycophenolic acid is reported to provide effective immunosuppression by inhibiting inosine monophosphate dehydrogenase. In an attempt to monitor the biological effects of long-term therapy with mycophenolate mofetil, we measured levels of guanosine 5' triphosphate and adenosine 5' triphosphate in red blood cells (RBCs) of patients after heart transplantations.METHODS:
Fifty-two patients enrolled in the study were randomly assigned to one of two groups. Patients in the control group (n = 27) received cyclosporine A (INN, ciclosporin), azathioprine, and prednisone. Patients in the study group (n = 25) were switched from azathioprine to mycophenolate mofetil 3 months after the heart transplantation. Adenosine 5' triphosphate and guanosine 5' triphosphate levels were determined by means of HPLC. The activities of inosine monophosphate dehydrogenase and hypoxanthine-guanine phosphoribosyltransferase, which are responsible for guanine nucleotide formation, were measured in RBCs by radiochemical methods.RESULTS:
Adenosine 5' triphosphate levels were unchanged in patients treated with mycophenolate mofetil, whereas those of the control group who received azathioprine (from 142 +/- 26 pmol/10(6) RBCs to 165 +/- 25 pmol/10(6) RBCs; P <.001) increased. As the length of mycophenolate mofetil therapy increased, patients in the study group showed significantly elevated guanosine 5' triphosphate levels (15.6 +/- 6.1 pmol/10(6) RBCs versus 6.6 +/- 2.1 pmol/10(6) RBCs; P <.001) and a 5-fold increase in inosine monophosphate dehydrogenase activity (108.6 +/- 13.3 pmol/mg of protein per hour versus 22.5 +/- 1.7 pmol/mg of protein per hour; P <.001) compared with the control group. In addition, a slight but significant enhancement of hypoxanthine-guanine phosphoribosyltransferase activity was seen in the mycophenolate mofetil group.CONCLUSIONS:
Our studies have shown that long-term administration of mycophenolate mofetil is associated with increasing guanosine 5' triphosphate levels in RBCs as the result of an induction of inosine monophosphate dehydrogenase and hypoxanthine-guanine phosphoribosyltransferase activities in erythrocytes.
Buscar no Google
Bases de dados:
MEDLINE
Assunto principal:
Azatioprina
/
Indução Enzimática
/
Transplante de Coração
/
Inibidores Enzimáticos
/
Guanosina Trifosfato
/
Imunossupressores
/
IMP Desidrogenase
/
Ácido Micofenólico
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Áustria