Effect of orlistat on blood cyclosporin concentration in an obese heart transplant patient.
OBJECTIVE
We detected markedly decreased cyclosporin blood levels in a heart-transplanted patient after the gastrointestinal lipase inhibitor orlistat was accidentally added to the treatment program to control for his obesity. Therefore, we determined cyclosporin plasma concentration time kinetics with and without orlistat reexposition in this patient.


METHODS
Plasma concentration time kinetics of whole blood cyclosporin levels in an obese heart-transplant patient were measured using a standard monoclonal fluorescence polarisation immunoassay. Results were obtained in hourly intervals up to 12 h without and with co-therapy of 3 x 120 mg orlistat (Xenical, Roche Ltd., Switzerland). The orlistat re-exposition was started the day before taking blood samples.


RESULTS
Cyclosporin trough levels (98 ng/ml vs 52 ng/ml), maximum concentrations (532 ng/ml vs 74 ng/ml) and the area under the blood drug concentration-time curve (2832 ng h ml-1 vs 700 ng h ml-1) were greatly reduced with orlistat.


CONCLUSIONS
Orlistat markedly decreased blood cyclosporin concentrations, possibly due to an interference with its absorption in the small intestine. To avoid potential dangerous under-immunosuppression, orlistat should not be used in patients taking cyclosporin.
Nägele
H
H
Abt. Thorax-Herz- und Gefässchirurgie, Universitäts-Krankenhaus Hamburg-Eppendorf, Germany. naegele@uke.uni-hamburg.de
Petersen
B
B
Bonacker
U
U
Rödiger
W
W
D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008049:Lipase / Q000037:antagonists & inhibitors; D008297:Male; D009765:Obesity / Q000150:complications* / Q000188:drug therapy; D000077403:Orlistat
D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007783:Lactones; D016572:Cyclosporine; D000077403:Orlistat; D008049:Lipase