The impact of long-term cyclosporin-A therapy on hematological and biochemical profile in renal transplant patients.

With over a decade of extensive clinical use of cyclosporin A (CsA), assessment of its long-term safety implications is due. In this study the impact of long-term continuous use of CsA on a number of hematological and biochemical parameters in renal transplant patients was evaluated. Two groups of 13 patients each, one on conventional therapy (azathioprine + prednisolone) and the other on triple therapy (azathioprine + prednisolone + CsA) for 4 to 15 years post-transplantation were compared with respect to their current and overall laboratory values and clinical outcome. Laboratory values were also compared with those of 23 matched healthy subjects. No significant difference in the clinical outcome was found between conventional and triple therapy groups, however, the triple therapy group had significantly less favorable mean values compared to the conventional therapy group with respect to hemoglobin (12.1 +/- 2.2 vs 13.3 +/- 2.1 g/dl, p < 0.02), hematocrit (0.36 +/- 0.06 vs 0.42 +/- 0.03 l/l, p < 0.05), urea (13.0 +/- 3.7 vs 6.7 +/- 4.3 mmol/l, p < 0.01) and uric acid (460.0 +/- 112 vs 330 +/- 88 mumol/l, p < 0.05). The increase in serum uric acid levels in the triple therapy group was progressive throughout the post-transplant period. For the 19 other parameters measured corresponding mean values in the 2 groups were comparable. Mean laboratory values for many parameters in both groups, however, still differed from those in the control group. These results showed that kidney transplant patients on long-term triple therapy have more hematological and biochemical abnormalities and no better clinical outcome than those on conventional therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesterification: an analytical and formulation problem.

A range of esters including salicylates, nicotinates and parabens have been shown to undergo reversible, base-catalysed transesterification in hydroalcoholic solutions. In non-alcoholic solution phenyl salicylate undergoes a concentration-dependent oligomerization which yields salsalate and other products. The transesterification reactions also occur in products formulated for topical use, which have vehicles based upon alcohol, glycol or glycol polymers. Without recognition, such reactions may compromise stability assessments, pharmaceutical integrity and delivery profiles.

Possible interaction between cyclosporine and glibenclamide in posttransplant diabetic patients.

The possible occurrence of a kinetic interaction between cyclosporine A and glibenclamide was assessed by reviewing data of six posttransplant diabetic patients who received the two drugs concurrently. Coadministration of the two drugs resulted in a 57% increase in the steady-state plasma cyclosporine levels despite normal hepatic and renal functions in the patients. This elevation in cyclosporine level is possibly due to an interaction between the two drugs resulting from an inhibition of CYP3A4-mediated metabolism of cyclosporine by glibenclamide. This observation calls for a closer monitoring of cyclosporine plasma levels during concomitant administration of these two drugs in this group of patients.