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Population pharmacokinetic analysis and dosing regimen optimization of aprotinin in neonates and young infants undergoing cardiopulmonary bypass.
MedLine Citation:
PMID:  20926755     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The objective of this study was to determine an optimal dosing regimen for maintaining the therapeutic target range of aprotinin in neonates and young infants during cardiopulmonary bypass (CPB). A total of 27 patients scheduled for open heart surgery were enrolled. Aprotinin was administered a 25 000 KIU (kallikrein inhibition unit)/kg bolus before operation, a 35 000 KIU/kg for CPB circuit priming, and a 12 500 KIU/kg/hour continuous infusion intra- and immediate postoperative period. Blood samples were obtained at 12 time points per patient. Population pharmacokinetic modeling and Monte-Carlo simulations were used to optimize the aprotinin dosing regimen. No mortality or aprotinin-related complication was encountered. A CPB adjusted 2-compartment model best fit the data. Clearance was 687 mL/hour during CPB and 350 mL/hour pre- and post-CPB, and corresponding volumes of distribution were 1577 mL and 1352 mL, respectively. The simulations conducted showed that more than twice the dose administered in this study is required to maintain the target concentration of aprotinin. The pharmacokinetics of aprotinin appears to be affected more sensitively by CPB in neonates and young infants than in adults. Therefore, dosage adjustment considering these pharmacokinetic differences and the influence of CPB is needed in neonates and young infants.
Authors:
You-Me Tae; Jae Gun Kwak; Bo-Hyung Kim; In-Jin Jang; Woong-Han Kim
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Publication Detail:
Type:  Journal Article     Date:  2010-10-06
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  51     ISSN:  1552-4604     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1163-76     Citation Subset:  IM    
Affiliation:
Department of Thoracic and Cardiovascular Surgery, Clinical Research Institute, Seoul National University College of Medicine, Seoul National University, Children's Hospital, 28 Yongon-Dong, Jongno-Gu, Seoul, 110-744, Republic of Korea; woonghan@snu.ac.kr.
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