Hepatic and intestinal CYP3A activity in cirrhotics with transjugular intrahepatic portosystemic shunts (TIPS)

J. C. Gorski, Naga Chalasani, N. Patel, R. E. Galinsky, R. Craven, S. D. Hall

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Abstract

TIPS catheters are used to treat severe variceal bleeding from portal hypertension. Intestinal and hepatic CYP3A activity was examined using the in vivo probe, midazolam (MDZ), in cirrhotics w/TIPS revision compared with stable cirrhotic patients and healthy volunteers. 9 cirrhotics (48±5 yrs), 9 cirrhotics w/TIPS (48±5 yrs) and 9 healthy volunteers (46±19 yrs) weighing 60-110kg received simultaneous IV and oral (PO) MDZ (0.05mg/kg) and 3 mg 15N3-MDZ, respectively. Serum samples were assayed for MDZ and metabolites using LC/MS. The clearance (CL) and component availabilities (F) are presented in Table 1. Cirrhosis significantly altered hepatic CYP3A activity but not intestinal CYP3A activity. Additionally, cirrhotics with TIPS demonstrated increased gut wall availability suggesting alterations in either CYP3A activity or intestinal wall per-meability. Table 1. TIPS Cirrhotics Volunteers CLIv (1/hr/kg) 0.2±0.1c 0.2±0.1c 0.4±0.1 CLPO (1/hr/kg) 0.3±0.2c 1.0±0.8a 1.5±0.4 FPO 0.8±0.2c 0.3±0.1a 0.3±0.1 FHepatic 0.9±0.06c 0.9±0.03c 0.7±0.1 FGut wall 0.9±0.3c 0.3±0.2a 0.4±0.2 a(p<0.05) compared to cirrhotics w/TIPS. c(p<0.05) compared to healthy volunteers.

Original languageEnglish
JournalClinical Pharmacology and Therapeutics
Volume69
Issue number2
StatePublished - 2001

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Transjugular Intrahepatic Portasystemic Shunt
Cytochrome P-450 CYP3A
Midazolam
Liver
Healthy Volunteers
Portal Hypertension
Volunteers
Fibrosis
Catheters
Hemorrhage
Serum

ASJC Scopus subject areas

  • Pharmacology

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Hepatic and intestinal CYP3A activity in cirrhotics with transjugular intrahepatic portosystemic shunts (TIPS). / Gorski, J. C.; Chalasani, Naga; Patel, N.; Galinsky, R. E.; Craven, R.; Hall, S. D.

In: Clinical Pharmacology and Therapeutics, Vol. 69, No. 2, 2001.

Research output: Contribution to journalArticle

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abstract = "TIPS catheters are used to treat severe variceal bleeding from portal hypertension. Intestinal and hepatic CYP3A activity was examined using the in vivo probe, midazolam (MDZ), in cirrhotics w/TIPS revision compared with stable cirrhotic patients and healthy volunteers. 9 cirrhotics (48±5 yrs), 9 cirrhotics w/TIPS (48±5 yrs) and 9 healthy volunteers (46±19 yrs) weighing 60-110kg received simultaneous IV and oral (PO) MDZ (0.05mg/kg) and 3 mg 15N3-MDZ, respectively. Serum samples were assayed for MDZ and metabolites using LC/MS. The clearance (CL) and component availabilities (F) are presented in Table 1. Cirrhosis significantly altered hepatic CYP3A activity but not intestinal CYP3A activity. Additionally, cirrhotics with TIPS demonstrated increased gut wall availability suggesting alterations in either CYP3A activity or intestinal wall per-meability. Table 1. TIPS Cirrhotics Volunteers CLIv (1/hr/kg) 0.2±0.1c 0.2±0.1c 0.4±0.1 CLPO (1/hr/kg) 0.3±0.2c 1.0±0.8a 1.5±0.4 FPO 0.8±0.2c 0.3±0.1a 0.3±0.1 FHepatic 0.9±0.06c 0.9±0.03c 0.7±0.1 FGut wall 0.9±0.3c 0.3±0.2a 0.4±0.2 a(p<0.05) compared to cirrhotics w/TIPS. c(p<0.05) compared to healthy volunteers.",
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AU - Hall, S. D.

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N2 - TIPS catheters are used to treat severe variceal bleeding from portal hypertension. Intestinal and hepatic CYP3A activity was examined using the in vivo probe, midazolam (MDZ), in cirrhotics w/TIPS revision compared with stable cirrhotic patients and healthy volunteers. 9 cirrhotics (48±5 yrs), 9 cirrhotics w/TIPS (48±5 yrs) and 9 healthy volunteers (46±19 yrs) weighing 60-110kg received simultaneous IV and oral (PO) MDZ (0.05mg/kg) and 3 mg 15N3-MDZ, respectively. Serum samples were assayed for MDZ and metabolites using LC/MS. The clearance (CL) and component availabilities (F) are presented in Table 1. Cirrhosis significantly altered hepatic CYP3A activity but not intestinal CYP3A activity. Additionally, cirrhotics with TIPS demonstrated increased gut wall availability suggesting alterations in either CYP3A activity or intestinal wall per-meability. Table 1. TIPS Cirrhotics Volunteers CLIv (1/hr/kg) 0.2±0.1c 0.2±0.1c 0.4±0.1 CLPO (1/hr/kg) 0.3±0.2c 1.0±0.8a 1.5±0.4 FPO 0.8±0.2c 0.3±0.1a 0.3±0.1 FHepatic 0.9±0.06c 0.9±0.03c 0.7±0.1 FGut wall 0.9±0.3c 0.3±0.2a 0.4±0.2 a(p<0.05) compared to cirrhotics w/TIPS. c(p<0.05) compared to healthy volunteers.

AB - TIPS catheters are used to treat severe variceal bleeding from portal hypertension. Intestinal and hepatic CYP3A activity was examined using the in vivo probe, midazolam (MDZ), in cirrhotics w/TIPS revision compared with stable cirrhotic patients and healthy volunteers. 9 cirrhotics (48±5 yrs), 9 cirrhotics w/TIPS (48±5 yrs) and 9 healthy volunteers (46±19 yrs) weighing 60-110kg received simultaneous IV and oral (PO) MDZ (0.05mg/kg) and 3 mg 15N3-MDZ, respectively. Serum samples were assayed for MDZ and metabolites using LC/MS. The clearance (CL) and component availabilities (F) are presented in Table 1. Cirrhosis significantly altered hepatic CYP3A activity but not intestinal CYP3A activity. Additionally, cirrhotics with TIPS demonstrated increased gut wall availability suggesting alterations in either CYP3A activity or intestinal wall per-meability. Table 1. TIPS Cirrhotics Volunteers CLIv (1/hr/kg) 0.2±0.1c 0.2±0.1c 0.4±0.1 CLPO (1/hr/kg) 0.3±0.2c 1.0±0.8a 1.5±0.4 FPO 0.8±0.2c 0.3±0.1a 0.3±0.1 FHepatic 0.9±0.06c 0.9±0.03c 0.7±0.1 FGut wall 0.9±0.3c 0.3±0.2a 0.4±0.2 a(p<0.05) compared to cirrhotics w/TIPS. c(p<0.05) compared to healthy volunteers.

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