ELIZA

return kwic search for through out of >500 occurrences
437431 occurrences (No.38 in the rank) during 5 years in the PubMed. [cache]

172) SIGNIFICANCE STATEMENT: Through both mass balance and semi-physiologically based pharmacokinetic (semi-PBPK) modeling approaches, this study mechanistically and quantitatively elucidates maribavir's enterohepatic recirculation (EHR) behavior in monkeys, which occurs via extensive direct glucuronidation, biliary secretion of these glucuronides, luminal hydrolysis of glucuronides to parent, and subsequent reabsorption of the parent.

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PMID:34462268 DOI:10.1124/dmd.121.000493

2021 Drug metabolism and disposition: the biological fate of chemicals

* Elucidation of Metabolic and Disposition Pathways for Maribavir in Nonhuman Primates through Mass Balance and Semi-Physiologically Based Modeling Approaches.

- Maribavir is in phase 3 clinical development for treatment of cytomegalovirus infection/disease in transplant recipients. Previous research conducted using only intact cynomolgus monkeys indicated biliary secretion as the primary elimination pathway for maribavir and that maribavir undergoes enterohepatic recirculation (EHR). To clarify the exact mechanisms of maribavir's EHR behavior, we studied its clearance pathways using intravenously administered ¹⁴C-labeled maribavir in intact and bile duct-cannulated (BDC) monkeys and constructed a semi-physiologically based pharmacokinetic (PBPK) model. Total radioactivity metabolite profiles in plasma and excreta were quantitatively determined along with plasma maribavir concentrations. Intact animals showed significantly lower clearance and longer half-lives in both total radioactivity and parent concentration in plasma than BDC monkeys. The primary in vitro and in vivo metabolic pathway for maribavir in monkey is direct glucuronidation; N-dealkylation and renal clearance are minor pathways. In BDC monkeys, 73% of dose was recovered as maribavir glucuronides in bile, and 3% of dose was recovered as parent in bile and feces; in intact animals' feces, 58% of dose was recovered as parent, and no glucuronides were detected. Therefore, EHR of maribavir occurs through biliary secretion of maribavir glucuronides, and this is followed by hydrolysis of glucuronides in the gut lumen and subsequent reabsorption of parent. A semi-PBPK model constructed from physiologic, in vitro, and in vivo BDC monkey data is capable of projecting maribavir's pharmacokinetic and EHR behavior in intact animals after intravenous or oral dosing and could be applied to modeling other xenobiotics that are subject to similar EHR processes. SIGNIFICANCE STATEMENT: Through both mass balance and semi-physiologically based pharmacokinetic (semi-PBPK) modeling approaches, this study mechanistically and quantitatively elucidates maribavir's enterohepatic recirculation (EHR) behavior in monkeys, which occurs via extensive direct glucuronidation, biliary secretion of these glucuronides, luminal hydrolysis of glucuronides to parent, and subsequent reabsorption of the parent. The study also identifies important drug- and animal-specific parameters that determine the EHR kinetics, and the semi-PBPK model is readily applicable to other drugs that undergo similar metabolic and recirculation mechanisms.

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[frequency of next (right) word to through]

(1)82 the	(13)3 discussion	(25)2 Google	(37)2 improving
(2)42 a	(14)3 food	(26)2 MEDLINE,	(38)2 induction
(3)8 an	(15)3 information	(27)2 Medline,	(39)2 lipid
(4)8 this	(16)3 inhibition	(28)2 PubMed	(40)2 multiple
(5)7 which	(17)3 its	(29)2 PubMed,	(41)2 nutrition
(6)6 resolution	(18)3 modulation	(30)2 abutment	(42)2 providing
(7)4 October	(19)3 searches	(31)2 analysis	(43)2 reference
(8)4 different	(20)3 several	(32)2 assessment	(44)2 semi-structured
(9)4 various	(21)3 their	(33)2 binding	(45)2 simulation
(10)3 January	(22)3 these	(34)2 dual	(46)2 specific
(11)3 July	(23)2 April	(35)2 gap	(47)2 thematic
(12)3 both	(24)2 August	(36)2 genetic

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--- WordNet output for through --- =>直通の, のために, の間じゅう, 終わって, を貫いて, の中を通って, のいたるところに, を通じて Overview of adj through The adj through has 2 senses (first 1 from tagged texts) 1. (4) done, through, through with -- (having finished or arrived at completion; "certain to make history before he's done"; "it's a done deed"; "after the treatment, the patient is through except for follow-up"; "almost through with his studies") 2. through -- ((of a route or journey etc.) continuing without requiring stops or changes; "a through street"; "a through bus"; "through traffic") Overview of adv through The adv through has 5 senses (first 3 from tagged texts) 1. (5) through -- (from beginning to end; "read this book through") 2. (2) through -- (over the whole distance; "this bus goes through to New York") 3. (1) through -- (to completion; "think this through very carefully!") 4. through -- (in diameter; "this cylinder measures 15 inches through") 5. through, through and through -- (throughout the entire extent; "got soaked through in the rain"; "I'm frozen through"; "a letter shot through with the writer's personality"; "knew him through and through"; "boards rotten through and through") --- WordNet end ---