Case Report: Azathioprine: An Old and Wronged Immunosuppressant.

Mycophenolate rapidly substituted azathioprine (AZA) in transplant immunosuppression regimens since the 1990s, when early clinical trials indicated better outcomes, although opposite results were also observed. However, none of these trials used the well-established optimization methods for AZA dosing, namely, thiopurine methyltransferase pharmacogenetics combined with monitoring of the thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). Resistance to optimize AZA therapy remains today in transplant therapy, despite the fact that thiopurine metabolite testing is being used by other medical disciplines with evident improvement in clinical results. In a previous analysis, we found that active 6-TGN metabolites were not detectable in about 30% of kidney transplant patients under continuous use of apparently adequate azathioprine dosage, which demonstrates the need to monitor these metabolites for therapeutic optimization. Two of four case studies presented here exemplifies this fact. On the other hand, some patients have toxic 6-TGN levels with a theoretically appropriate dose, as seen in the other two case studies in this presentation, constituting one more important reason to monitor the AZA dose administered by its metabolites. This analysis is not intended to prove the superiority of one immunosuppressant over another, but to draw attention to a fact: there are thousands of patients around the world receiving an inadequate dose of azathioprine and, therefore, with inappropriate immunosuppression. This report is also intended to draw attention, to clinicians using thiopurines, that allopurinol co-therapy with AZA is a useful therapeutic pathway for those patients who do not adequately form active thioguanine metabolites.

Effects of long-term administration of omeprazole on bone mineral density and the mechanical properties of the bone.

OBJECTIVES: Epidemiological studies have shown a relationship between long-term use of proton pump inhibitors and bone metabolism. However, this relationship has not yet become established. The aim of the present study was to analyze the mechanical properties and bone mineral density (BMD) of rats that were subjected to long-term omeprazole use. METHODS: Fifty Wistar rats weighing between 200 and 240 g were divided equally into five groups: OMP300 (omeprazole intake at a dose of 300 µmoL/kg/day); OMP200 (200 µmoL/kg/day); OMP40 (40 µmoL/kg/day); OMP10 (10 µmoL/kg/day); and Cont (control group; intake of dilution vehicle). The solutions were administered for 90 consecutive days. After the rats had been sacrificed, their BMD, the mechanical properties of the dissected femurs and their serum Ca++ levels were analyzed. RESULTS: The BMD of the OMP300 group was lower than that of the controls (p = 0.006). There was no difference on comparing the OMP200, OMP40 and OMP10 groups with the controls. The maximum strength and rigidity of the femur did not differ in the experimental groups in comparison with the controls. The OMP300 group had a statistically lower serum Ca++ concentration than that of the controls (p = 0.049), but the other groups did not show any difference in relation to the controls. CONCLUSION: Daily intake of 300 µmoL/kg/day of omeprazole decreased the BMD of the femur, but without changes to the rigidity and strength of the femur in adult rats.

OBJETIVOS: Estudos epidemiológicos mostram uma relação entre o uso em longo prazo de inibidores de bomba de prótons e o metabolismo ósseo, porém essa relação ainda não está estabelecida. O objetivo deste estudo foi analisar as propriedade mecânicas e a densidade mineral óssea (DMO) de ratos submetidos ao uso de omeprazol em longo prazo. MÉTODOS: Cinquenta ratos Wistar, entre 200 e 240 g, foram divididos igualmente em cinco grupos: OMP300 (ingestão de omeprazol na dose de 300 µmoL/Kg/dia), OMP200 (200 µmoL/Kg/dia), OMP40 (40 µmoL/Kg/dia), OMP10 (10 µmoL/Kg/dia) e Cont (grupo controle; ingestão do veículo de diluição). A administração das soluções ocorreu durante 90 dias seguidos. Após a eutanásia, foram analisadas a DMO, as propriedades mecânicas dos fêmures dissecados e a dosagem de Ca++ sérico. RESULTADOS: A DMO do grupo OMP300 foi menor do que a do Cont (p = 0,006). Não houve diferença na comparação entre os grupos OMP200, OMP40 e OMP10 em relação ao Cont. A força máxima e rigidez do fêmur não foram diferentes nos grupos experimentais quando comparados ao Cont. O grupo OMP300 teve concentrações séricas de Ca++ estatisticamente menores do que o grupo Cont (p = 0,049) sem diferença entre os demais grupos em relação ao Cont. CONCLUSÃO: A ingestão diária de 300 µmoL/Kg/dia de omeprazol diminuiu a DMO do fêmur, porém sem alterações na rigidez e na força do fêmur de ratos adultos.