Enterohepatic recirculation of the new antihypertensive drug UP 269-6 in humans. A possible model to account for multiple plasma peaks
- PMID: 9541723
Enterohepatic recirculation of the new antihypertensive drug UP 269-6 in humans. A possible model to account for multiple plasma peaks
Abstract
Following a single dose of a new antihypertensive drug, UP 269-6 (5-methyl-7-propyl-8-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl]-1,2,4-triazolo[1,5-c]pyrimidin-2(3H)-one, CAS 148504-51-2), to 12 healthy volunteers, the plasma levels showed at least two secondary peaks. To explain this observation, the data were fitted to a new compartmental model of enterohepatic recirculation, without using a numerical method. Most subjects exhibited two cycles of recirculation. The amount of drug involved in each recirculation was calculated and the AUCs compared. The drug showed high biliary excretion and reabsorption.
Similar articles
-
Population Pharmacokinetic Modeling of the Enterohepatic Recirculation of Fimasartan in Rats, Dogs, and Humans.AAPS J. 2015 Sep;17(5):1210-23. doi: 10.1208/s12248-015-9764-2. Epub 2015 May 20. AAPS J. 2015. PMID: 25990964 Free PMC article. Clinical Trial.
-
Characterizing the time-course of antihypertensive activity and optimal dose range of fimasartan via mechanism-based population modeling.Eur J Pharm Sci. 2017 Sep 30;107:32-44. doi: 10.1016/j.ejps.2017.06.008. Epub 2017 Jun 7. Eur J Pharm Sci. 2017. PMID: 28599987 Clinical Trial.
-
Population pharmacokinetic modeling for enterohepatic recirculation in Rhesus monkey.Eur J Pharm Sci. 2005 Oct;26(2):151-61. doi: 10.1016/j.ejps.2005.05.010. Eur J Pharm Sci. 2005. PMID: 16085400
-
A population pharmacokinetic model that describes multiple peaks due to enterohepatic recirculation of ezetimibe.Clin Ther. 2001 Jun;23(6):871-85. doi: 10.1016/s0149-2918(01)80075-8. Clin Ther. 2001. PMID: 11440287 Clinical Trial.
-
Prediction of human pharmacokinetics-biliary and intestinal clearance and enterohepatic circulation.J Pharm Pharmacol. 2008 May;60(5):535-42. doi: 10.1211/jpp.60.5.0001. J Pharm Pharmacol. 2008. PMID: 18416932 Review.
Cited by
-
Enterohepatic circulation: physiological, pharmacokinetic and clinical implications.Clin Pharmacokinet. 2002;41(10):751-90. doi: 10.2165/00003088-200241100-00005. Clin Pharmacokinet. 2002. PMID: 12162761 Review.
-
Multiple peaking phenomena in pharmacokinetic disposition.Clin Pharmacokinet. 2010 Jun;49(6):351-77. doi: 10.2165/11319320-000000000-00000. Clin Pharmacokinet. 2010. PMID: 20481648 Review.
-
Intestinal transport as a potential determinant of drug bioavailability.Curr Clin Pharmacol. 2013 Aug;8(3):247-55. doi: 10.2174/1574884711308030012. Curr Clin Pharmacol. 2013. PMID: 23343017 Free PMC article. Review.
-
A recirculatory model with enterohepatic circulation by measuring portal and systemic blood concentration difference.J Pharmacokinet Pharmacodyn. 2003 Apr;30(2):119-44. doi: 10.1023/a:1024415730100. J Pharmacokinet Pharmacodyn. 2003. PMID: 12942684
Publication types
MeSH terms
Substances
LinkOut - more resources
Medical