Pharmacokinetics of cyclosporin A during pregnancy; monitoring of treatment and specific assays of cyclosporin, based on five liver transplant patients.
Very little information is available concerning the pharmacokinetic behaviour and monitoring of cyclosporin A (CsA) during pregnancy, notably after liver transplant. Monitoring of blood levels of CsA is considered to be one of the best tools for evaluation of the efficacy of immunosuppressant treatment. The aim of this study was to bring together new information concerning pregnant women receiving immunosuppressant treatment with CsA and, in view of the special pathophysiological status of such patients, to compare pharmacokinetic profiles of changes in blood levels of CsA and of the combination of CsA plus metabolites. Specific (CsA-S kit) and a new non-specific (CsA-NS kit) assays of CsA were carried out in five hospitalized pregnant patients who had received liver transplants between the 6th and the 41st weeks of amenorrhea. The results of five cases investigated lead to the following conclusions: (1) The pharmacokinetic behaviour of native CsA in the pregnant woman between the 6th and 41st weeks of amenorrhea suggests no systemic accumulation nor any radical need for changes in dosage schedule as compared with a non-pregnant patient. (2) Monitoring based upon simultaneous use of the CsA-NS and CsA-S kits may be a source of analytical bias and hence confusion for the physician. (3) Determination of an experimental CsA-NS/CsA-S accumulation ratio (based upon analysis of single concentrations or processing of AUCs) is of interest only if specific assays involve not only CsA itself but also its principal metabolites. (4) Monitoring based upon single measurements of residual CsA levels only, is necessary and adequate. Furthermore, such an approach is less costly.(ABSTRACT TRUNCATED AT 250 WORDS)
Bourget
P
P
Laboratory of Pharmacology and Toxicology, Hôpital Antoine Beclere, Clamart, France.
Fernandez
H
H
Quinquis
V
V
Delouis
C
C
D000328:Adult; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D011247:Pregnancy / Q000097:blood*
D016572:Cyclosporine