Immunosuppressive drugs and pregnancy: Experimental and clinical data

Abstract THE REASONED choice of a drug results from the double evaluation of the expected benefit and the subsequent therapeutic risks. This becomes obviously more complicated when several drugs have to be given in combination for better effectiveness, as is the case for transplant patients. Therapeutic risks are therefore increased because either the side effects are the same in nature and act synergistically, or they simply become more numerous. They are also enhanced when drug indications coincide with particular conditions, one of them being pregnancy, which no doubt becomes a condition at risk in all transplant women. One has then to face the triple challenge to combine successfully altogether a right level of immunosuppression, a pregnancy that would work out normally, and the absence of fetal damage. A specific procedure does not exist today to systematically study what could be entitled a school's case of pharmacology. In fact, immunosuppressive treatments are established most of the time on the basis of empirical results, which means that there is only a narrow margin left for an attempt to modify therapeutic protocols that have been already stated that way. Immunosuppressant drugs also frequently, even constantly, develop side effects such as renal insufficiency and hypertension in the mother and prematurity in the fetus. With that in mind, we here will state the pharmacological basis for the use of immunosuppressants in posttransplant pregnant women, in order to provide not only for the mother's safety but also to prevent both the fetus (F 1 ) and second generation (F 2 ) from drug injury. In that view, we have designed a step-by-step critical analysis that addresses the various pharmacological parameters of immunosuppressants that may be used during pregnancy. Our evaluation has been made on the basis of toxicologic, pharmacodynamic, and pharmacokinetic criteria in the light of pregnancy itself and its most frequently associated pathological states.