title: Increased Renal Clearance of Rocuronium Compensates for Chronic Loss of Bile Excretion, via upregulation of Oatp2.
abstract: Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation.
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anaesthesiology, 101th Hospital of Chinese People's Liberation Army, 101 North Xingyuan Road, Wuxi, Jiangsu, China.
authors.forename: Mai-Tao
authors.initials: MT
authors.lastname: Zhou
authors.affiliation: Department of Anaesthesiology, 101th Hospital of Chinese People's Liberation Army, 101 North Xingyuan Road, Wuxi, Jiangsu, China.
authors.forename: Cai-Yang
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Anaesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Anaesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China.
authors.forename: Da-Xiang
authors.initials: DX
authors.lastname: Wen
authors.affiliation: Department of Anaesthesiology, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Cheung
authors.affiliation: Department of Anaesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Yang
authors.affiliation: Department of Anaesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, 225 Changhai Road, Shanghai, China.|Department of Anaesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pudian Road, Shanghai, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Yu
mesh_terms: D000732:Androstanols / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000378:metabolism / Q000473:pathology; D002648:Child; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D041781:Jaundice, Obstructive / Q000473:pathology; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008297:Male; D027361:Organic Anion Transporters / Q000378:metabolism*; D000077123:Rocuronium; D015854:Up-Regulation
chemical_list: D000732:Androstanols; D027361:Organic Anion Transporters; C503597:Slco1a4 protein, rat; D000077123:Rocuronium