Cyclosporine bioavailability: dosing implications and impact on clinical outcomes in select transplantation...

Reports in the literature indicate that clinical outcomes in select patient subpopulations have been inferior to those in the general transplantation population. Of potential interest in this regard is the finding that lower cyclosporine bioavailability correlates with a higher incidence of acute rejection and graft loss. To gain insights into these issues, we examined data from renal transplant recipients at our own centers and in one large data base. Our experience revealed that cyclosporine bioavailability was markedly lower in patients who developed acute or chronic rejection than in those with stable graft function. An analysis by demographic or clinical factors showed that cyclosporine bioavailability was lower in diabetics and black patients. In one study, diabetics required much higher daily doses of cyclosporine to achieve outcomes comparable to those in non-diabetics; even then, diabetics attained lower cyclosporine blood levels. Other work found that long-term graft survival rates were poorer in blacks, even though cyclosporine dosages and blood levels were comparable to those in whites. A case-controlled study from the pregnancy registry found that cyclosporine 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 absorption, resulting in more consistent and predictable cyclosporine bioavailability.