Andrews, W

Iwatsuki, S

Shaw, BW

Starzl, TE

English

Shaw Jr, BW

Name not available

Bile diversion and cyclosporine dosage (Letter)

D-Scholarship@Pitt

After liver transplantation, there are marked variations in the enteral absorption of cyclosporine, as judged by whole-blood cyclosporine concentrations measured with radioimmu-noassay (1, 2). The absorption is influenced by the presence or absence of external bile drainage, a clinically significant factor that can be demonstrated by describing a few cases of the many that have been encountered. Case No.1. A 36-year-old woman who had an orthotopic liver transplantation for cholangiocarcinoma, returned more than a year later with a rising serum bilirubin. A percutaneous cholan-giocatheter was inserted, which drained significant amounts of bile. Without changing Qer oral cyclosporine dosage, the blood cyclosporine level fell over 48 hr from 991 nglml, to 362 nglml. The blood cyclosporine level remained in the 300-500 nglml range until the tube was clamped, at which time it increased from 676 nglml to 1,126 nglml, again without changing the oral cyclo$porine dose. (Fig. n Case No.2. A 38-year-old mim who underwent an orthotopic liver transplantation 8 months earlier was admitted because of recurrent fevers and a rising serum bilirubin. Ultrasound ex-amination showed common bile duct dilatation; a percutaneous biliary catheter was inserted. The blood cyclosporine level before percutaneous tube insertion was 1,023 ng/ml. Twenty-four hours after biliary drainage, the cyclosporine concentra-tion fell to 459 ng/m!. The level remained between 200 and 500 nglml despite increasing his daily oral dose from 480 mg to 1,200 mg (Fig. 1). Dilatation of a biliary stricture was performed under radiographic control, and eventually the drainage tube was clamped and removed. After the tube was clamped, the woocu_'_'_' _____ ~ __ cI_~_os_~_D~ __ ll_M_D_~_a_KI_D_~ ______ __ ClA"'P·I'l'_" TUAf: '000 I E 2000 co < ~ 2000 CASI '2 ~~------------------------------------~Doog > .. ~ "' z,ooo i CVClOSl'OAINI DOll 1""'0 ... "1 ~1Dnl ..... faa+-f~fftl~-D ... _--_ ,. " o a. E ~ I~~ ____ ~ __ ...... iiii"lcim~ .. =-.... ~~~~ g r'cog g ~ K~ u "Dv~I~!!K~ - I , -.0} ~I~ '; ~ 3 oC 5 6 7 8 • '0 11 12 13 ,,, 15 16 17 18 " 20 21 22 24 25 0 a~p FIGURE 1. The influence of biliary tube insertion, opening, or clamping in three patients, \'01. :\'1, \" , "',"I,d 'n I \ ~ Transplantation LEDER TO_ EDITOR cyclosporine concentration increased from 247 nglml to 1:«1 ng/m\ over 48 hr, necessitating a major downward revision in the daily oral dosage. Case No.3. A 56-year-old man had his T tube clamped 311z days after orthotopic liver transplantation. He had already begun cyclosporine bY,the oral route, and had resumed a diet. The blood level of cyclosporine rose over the next 24 hr to the toxic level of 2,251 nglml (Fig. 1). His serum transaminaaea and BUN increased, and he developed malaise and upper ex. tremity tremors. His T tube was un clamped and his blood cyclosporine level fell precipitously over the next 3 days. Later his T tube was clamped ~gain before its removal, with a prompt tripling of the cyclosporine blood level (Fig. 1). The correlation between cutaneous bile diversion and whole. blood cyclosporine levels is well shown in these 3 examples, and can be demonstrated quite clearly in virtually every similar case. Because cyclosporine is fat-soluble, its efficient absorption presumably is dependent -on the bile salts that are removed with bile diversion. - At one time, 'it was thought th~t cyclosporine h-ad a signifi-cant en~rohepatic circulation (3). If so, interruption of this cycle could be a factor. However, recent studies by Venkatara. manan et al. (2) have shown the enterohepatic circulation of cyclosporine to be toO minor to account for the major effect of bile diversion herein described. Whatever the explanation, adjustments in cyclosporine dos-age must be considered whenever external bile diversion is instituted or discontinued. The changes are best guided by pharmacologic monitoring. 338 WALT ANDREWS SHUNZABURO }WATSUKI BYERS W. SHAW, JR. THOMAS E. STARZL DepartmRnt of Surgery University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania 15261 REFERENCES 1. Burckart G, Stanl T. Williams L. et al. Cyciosporine monitoring and pharmacokinetics in pediatric liver transplant patients. Transplant Proc (in press): 2,. Venkataramanan R. Stanl TE, Yang S, et al. Biliary excretion of cyclosporine in liver transplant patients. Transplant Proc (in press). 3. Kahan BD, Ried M. Newburger J. Pharmacokinetics of cyclo· sporine in human renaLtransplantation. Transplant Proc 1983;' 15: 446. 

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Bile diversion and cyclosporine dosage (Letter)

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