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return kwic search for rate out of >500 occurrences
286534 occurrences (No.87 in the rank) during 5 years in the PubMed. [cache]

379) These models were parameterized using rate equations and numerical solutions of the ordinary differential equations.

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PMID:34503953 DOI:10.1124/dmd.121.000554

2021 Drug metabolism and disposition: the biological fate of chemicals

* Complex Cytochrome P450 Kinetics Due to Multisubstrate Binding and Sequential Metabolism. Part 2. Modeling of Experimental Data.

- Three CYP3A4 substrates, midazolam, ticlopidine, and diazepam, display non-Michaelis-Menten kinetics, form multiple primary metabolites, and are sequentially metabolized to secondary metabolites. We generated saturation curves for these compounds and analyzed the resulting datasets using a number of single-substrate and multisubstrate binding models. These models were parameterized using rate equations and numerical solutions of the ordinary differential equations. Multisubstrate binding models provided results superior to single-substrate models, and simultaneous modeling of multiple metabolites provided better results than fitting the individual datasets independently. Although midazolam datasets could be represented using standard two-substrate models, more complex models that include explicit enzyme-product complexes were needed to model the datasets for ticlopidine and diazepam. In vivo clearance predictions improved markedly with the use of in vitro parameters from the complex models versus the Michaelis-Menten equation. The results highlight the need to use sufficiently complex kinetic schemes instead of the Michaelis-Menten equation to generate accurate kinetic parameters. SIGNIFICANCE STATEMENT: The metabolism of midazolam, ticlopidine, and diazepam by CYP3A4 results in multiple metabolites and sequential metabolism. This study evaluates the use of rate equations and numerical methods to characterize the in vitro enzyme kinetics. Use of complex cytochrome P450 kinetic models is necessary to obtain accurate parameter estimates for predicting in vivo disposition.

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(1)172 of	(10)5 that	(19)3 step	(28)2 increased
(2)40 and	(11)5 the	(20)2 (ESR),	(29)2 it
(3)32 was	(12)4 (HR),	(21)2 (RMR)	(30)2 lactate,
(4)31 null	(13)4 among	(22)2 after	(31)2 or
(5)24 in	(14)4 discrimination	(23)2 at	(32)2 respiratory
(6)8 variability	(15)4 is	(24)2 attributable	(33)2 to
(7)6 constants	(16)4 were	(25)2 between	(34)2 top
(8)6 for	(17)3 enzyme	(26)2 constant	(35)2 which
(9)5 (HR)	(18)3 on	(27)2 equations

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--- WordNet output for rate --- =>価格を評定する, 割合, 率, 歩合, 料金, 値段, 相場, 速度, 度合, 人を〜を思う, みなす, 価値がある, 人を〜とみなす, 科金, 評価する Overview of noun rate The noun rate has 4 senses (first 3 from tagged texts) 1. (68) rate -- (a magnitude or frequency relative to a time unit; "they traveled at a rate of 55 miles per hour"; "the rate of change was faster than expected") 2. (39) rate, charge per unit -- (amount of a charge or payment relative to some basis; "a 10-minute phone call at that rate would cost $5") 3. (1) pace, rate -- (the relative speed of progress or change; "he lived at a fast pace"; "he works at a great rate"; "the pace of events accelerated") 4. rate -- (a quantity or amount or measure considered as a proportion of another quantity or amount or measure; "the literacy rate"; "the retention rate"; "the dropout rate") Overview of verb rate The verb rate has 3 senses (first 3 from tagged texts) 1. (9) rate, rank, range, order, grade, place -- (assign a rank or rating to; "how would you rank these students?"; "The restaurant is rated highly in the food guide") 2. (2) rate -- (be worthy of or have a certain rating; "This bond rates highly") 3. (1) rate, value -- (estimate the value of; "How would you rate his chances to become President?"; "Gold was rated highly among the Romans") --- WordNet end ---