Dose-adjusted cyclosporine c2 in a patient with jejunoileal bypass as compared to seven other liver transplant recipients.

摘要

Jejunoileal bypass (JIB) is a weight loss procedure in which malabsorption is produced by connecting a short length of proximal jejunum to the distal ileum. Because 90% of the small intestine is bypassed, it may have impact on the dose-concentration response of oral cyclosporine (CsA). The authors characterized the dose-adjusted blood concentrations of CsA obtained 2 hours (C2) after oral microemulsion CsA (ME-CsA) in a liver transplant (LTx) subject with an intact JIB, as compared with those from seven LTx controls without JIB. The biliary reconstruction involved choledochocholedochostomy without external drainage in all patients. ME-CsA was administered via a nasogastric tube within 24 hours after graft reperfusion. Oral fluconazole was given prophylactically to the study subject only for 6 days after LTx. During the first week after LTx, the dose-adjusted C2 (mean +/- SD) for the study subject and for controls was 53 +/- 10 and 106 +/- 47 ng/mL, respectively (P < 0.001). The corresponding value during the period from day 7 to day 107 was 105 +/- 40 and 257 +/- 86 ng/mL, respectively (P < 0.001). Multiple linear regression revealed that dosage, days after LTx, and the presence of a JIB were all independent predictors of C2 (R2 = 0.798, P = 0.037). Lack of bile resulting in malabsorption of ME-CsA was not thought to be significant contributor to her low dose-adjusted C2 because there was no external bile drainage and a portion of terminal ileum, where most bile acid reabsorption occurred, was still available after JIB. The fact that fluconazole failed to increase the dose-adjusted C2 in the study subject supports that enteric clearance of CsA may become clinically unimportant after JIB. Therefore, the low dose-adjusted C2 is most likely explained by the reduced bowel length and associated absorptive surface area after JIB. In conclusion, patients with JIB may require higher doses of ME-CsA.