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1.
Int J Clin Pharmacol Ther ; 41(10): 488-91, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14703956

RESUMO

The advent of new antidiabetic drugs is of special importance for diabetic patients with already impaired renal function since renal insufficiency is a relative or absolute contraindication for several of the established hypoglycemic drugs. Pioglitazone is a novel oral hypoglycemic agent that increases insulin responsiveness in target tissues. Pioglitazone and its active metabolites are excreted mainly via the liver. Drug exposure remains almost constant across a wide range of renal function since there is no accumulation of the drug or its active metabolites during repeated dosing in renal insufficiency. The pharmacokinetic properties of pioglitazone are ideally suited for patients with renal insufficiency. Although there are possible side effects (mainly fluid retention and weight gain and--very rarely--hepatotoxicity). Pioglitazone has a good safety profile in diabetic patients with impaired renal function.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Hipoglicemiantes , Tiazolidinedionas , Área Sob a Curva , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/metabolismo , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Taxa de Depuração Metabólica , Pioglitazona , Tiazolidinedionas/metabolismo , Tiazolidinedionas/farmacocinética , Tiazolidinedionas/uso terapêutico
2.
Transpl Int ; 13 Suppl 1: S311-3, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11112021

RESUMO

The novel immunosuppressive compound FTY 720A posseses a mode of action which is different from all other immunosuppressive drugs. The most prominent feature is a reversible decrease in peripheral lymphocyte counts observed in animal experiments. We investigated in the first human trial (phase 1) whether FTY 720A induces apoptosis of peripheral blood mononuclear cells (PBMC) in stable renal allograft recipients. Monitoring of lymphocyte counts revealed a significant and dose-dependent decrease within 6 h post-FTY 720A dose: placebo 5.1%; 0.25 mg 36.4%; 0.5 mg 40.8%; 0.75 mg 39.4%; 1 mg 45.8%; 2 mg 67.2%; 3.5 mg 64.9%. PBMC apoptosis rates did not change, as determined before intake of FTY 720A and 2 h, 6 h, 24 h and 96 h post-FTY 720A dose. We detected no significant difference in apoptosis rates between patients who received placebo or FTY 720A. However, in vitro experiments showed that high concentrations of FTY 720 A induced apoptosis in human PBMC.


Assuntos
Imunossupressores/farmacologia , Transplante de Rim/imunologia , Contagem de Linfócitos , Linfócitos/imunologia , Propilenoglicóis/farmacologia , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Cloridrato de Fingolimode , Humanos , Imunossupressores/administração & dosagem , Linfócitos/efeitos dos fármacos , Placebos , Propilenoglicóis/efeitos adversos , Esfingosina/análogos & derivados
3.
Am J Kidney Dis ; 35(3): E12, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10692297

RESUMO

The incidence of tuberculosis among transplant recipients is greater than in the general population. Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that has become part of most standard immunosuppressive protocols after renal transplantation. We have recently shown that conversion from azathioprine (AZA) to MMF in patients with chronic allograft dysfunction may be beneficial. Here, we report a patient with a history of pulmonary tuberculosis during his childhood. This patient was converted from AZA to MMF therapy 16 years after allogenic renal transplantation because of chronic allograft dysfunction. Two months later, he developed axillary lymph node tuberculosis caused by Mycobacterium tuberculosis. Because he denied contact with infectious persons, we diagnosed reactivation of old dormant tuberculosis. After surgical extirpation, quadruple antituberculous therapy was administered for 3 months (isoniazid, rifampicin, ethambutol, and pyrazinamide), followed by dual therapy for 3 months (isoniazid and rifampicin), and monotherapy for another 3 months (isoniazid). In the follow-up period, he remained asymptomatic with stable graft function. We conclude that MMF therapy in renal allograft recipients may cause reactivation of old dormant tuberculosis, even in the very late posttransplantation period. In these patients, close monitoring and isoniazid prophylaxis may be useful.


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/efeitos adversos , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Tuberculose dos Linfonodos/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Recidiva
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