CYCLOSPORINE BIOAVAILABILITY - DOSING IMPLICATIONS AND IMPACT ON CLINICAL OUTCOMES IN SELECT TRANSPLANTATION SUBPOPULATIONS

Reports in the literature indicate that clinical outcomes in select pa tient subpopulations have been inferior to those in the general transp lantation population. Of potential interest in this regard is the find ing that lower cyclosporine bioavailability correlates with a higher i ncidence of acute rejection and graft loss. To gain insights into thes e issues, we examined data from renal transplant recipients at our own centers and in one large data base. Our experience revealed that cycl osporine bioavailability was markedly lower in patients who developed acute or chronic rejection than in those with stable graft function. A n analysis by demographic or clinical factors showed that cyclosporine bioavailability was lower in diabetics and black patients. In one stu dy, diabetics required much higher daily doses of cyclosporine to achi eve outcomes comparable to those in non-diabetics; even then, diabetic s attained lower cyclosporine blood levels. Other work found that long -term graft survival rates were poorer in blacks, even though cyclospo rine dosages and blood levels were comparable to those in whites. A ca se-controlled study from the pregnancy registry found that cyclosporin e dosages were consistently higher in pregnant patients who maintained good graft function than in those who experienced graft dysfunction. These results suggest that the subpopulations examined should receive immunosuppression with higher cyclosporine dosages than those used in the general transplantation population. These subpopulations may also benefit from a cyclosporine formulation that provides better absorptio n, resulting in more consistent and predictable cyclosporine bioavaila bility.