ELIZA

return kwic search for time out of >500 occurrences
357929 occurrences (No.51 in the rank) during 5 years in the PubMed. [cache]

281) To account for age, we performed in vitro metabolism and time-dependent inhibition studies for solithromycin for CYP3A4, CYP3A5, and CYP3A7.

--- ABSTRACT ---

PMID:34154994 DOI:10.1124/dmd.120.000318

2021 Drug metabolism and disposition: the biological fate of chemicals

* Leveraging Physiologically Based Pharmacokinetic Modeling and Experimental Data to Guide Dosing Modification of CYP3A-Mediated Drug-Drug Interactions in the Pediatric Population.

- Solithromycin is a novel fluoroketolide antibiotic that is both a substrate and time-dependent inhibitor of CYP3A. Solithromycin has demonstrated efficacy in adults with community-acquired bacterial pneumonia and has also been investigated in pediatric patients. The objective of this study was to develop a framework for leveraging physiologically based pharmacokinetic (PBPK) modeling to predict CYP3A-mediated drug-drug interaction (DDI) potential in the pediatric population using solithromycin as a case study. To account for age, we performed in vitro metabolism and time-dependent inhibition studies for solithromycin for CYP3A4, CYP3A5, and CYP3A7. The PBPK model included CYP3A4 and CYP3A5 metabolism and time-dependent inhibition, glomerular filtration, P-glycoprotein transport, and enterohepatic recirculation. The average fold error of simulated and observed plasma concentrations of solithromycin in both adults (1966 plasma samples) and pediatric patients from 4 days to 17.9 years (684 plasma samples) were within 0.5- to 2.0-fold. The geometric mean ratios for the simulated area under the concentration versus time curve (AUC) extrapolated to infinity were within 0.75- to 1.25-fold of observed values in healthy adults receiving solithromycin with midazolam or ketoconazole. DDI potential was simulated in pediatric patients (1 month to 17 years of age) and adults. Solithromycin increased the simulated midazolam AUC 4- to 6-fold, and ketoconazole increased the simulated solithromycin AUC 1- to 2-fold in virtual subjects ranging from 1 month to 65 years of age. This study presents a systematic approach for incorporating CYP3A in vitro data into adult and pediatric PBPK models to predict pediatric CYP3A-mediated DDI potential. SIGNIFICANCE STATEMENT: Using solithromycin, this study presents a framework for investigating and incorporating CYP3A4, CYP3A5, and CYP3A7 in vitro data into adult and pediatric physiologically based pharmacokinetic models to predict CYP3A-mediated DDI potential in adult and pediatric subjects during drug development. In this study, minor age-related differences in inhibitor concentration resulted in differences in the magnitude of the DDI. Therefore, age-related differences in DDI potential for substrates metabolized primarily by CYP3A4 can be minimized by closely matching adult and pediatric inhibitor concentrations.

--- ABSTRACT END ---

[
right
kwic]

[frequency of next (right) word to time]

(1)48 and	(16)5 course	(31)3 inhibition	(46)2 indoors
(2)47 null	(17)5 when	(32)3 on	(47)2 interaction
(3)22 of	(18)4 TCD	(33)3 we	(48)2 interval
(4)16 in	(19)4 at	(34)2 across	(49)2 period,
(5)15 to	(20)4 curve	(35)2 after	(50)2 periods
(6)13 points	(21)4 point	(36)2 along	(51)2 points,
(7)10 the	(22)4 profiles	(37)2 between	(52)2 points:
(8)8 spent	(23)4 were	(38)2 can	(53)2 polymerase
(9)7 period	(24)4 with	(39)2 compared	(54)2 required
(10)7 that	(25)3 a	(40)2 concentration-,	(55)2 scale
(11)6 characteristics	(26)3 data	(41)2 constraints	(56)2 since
(12)6 for	(27)3 during	(42)2 cross-network	(57)2 sleepiness
(13)6 is	(28)3 frame	(43)2 functional	(58)2 using
(14)6 was	(29)3 frames	(44)2 guideline	(59)2 will
(15)5 PCR	(30)3 horizon	(45)2 inactivation

add keyword

--- WordNet output for time --- =>1.時代, 季節, 歳月, 当時, 現代, 一生, 年季, 就業時間, 期間, 時刻, 時点, 機会, 拍子, 速度, 何度, 何回, 時, 時間, 回, 2.時間[速度]を測定する, 時間を決める, (装置などの)タイミングを調節する Overview of noun time The noun time has 10 senses (first 9 from tagged texts) 1. (219) time, clip -- (an instance or single occasion for some event; "this time he succeeded"; "he called four times"; "he could do ten at a clip") 2. (160) time -- (a period of time considered as a resource under your control and sufficient to accomplish something; "take time to smell the roses"; "I didn't have time to finish"; "it took more than half my time") 3. (114) time -- (an indefinite period (usually marked by specific attributes or activities); "he waited a long time"; "the time of year for planting"; "he was a great actor in his time") 4. (43) time -- (a suitable moment; "it is time to go") 5. (36) time -- (the continuum of experience in which events pass from the future through the present to the past) 6. (10) time -- (a person's experience on a particular occasion; "he had a time holding back the tears"; "they had a good time together") 7. (7) clock time, time -- (a reading of a point in time as given by a clock; "do you know what time it is?"; "the time is 10 o'clock") 8. (5) fourth dimension, time -- (the fourth coordinate that is required (along with three spatial dimensions) to specify a physical event) 9. (1) meter, metre, time -- (rhythm as given by division into parts of equal duration) 10. prison term, sentence, time -- (the period of time a prisoner is imprisoned; "he served a prison term of 15 months"; "his sentence was 5 to 10 years"; "he is doing time in the county jail") Overview of verb time The verb time has 5 senses (first 3 from tagged texts) 1. (4) clock, time -- (measure the time or duration of an event or action or the person who performs an action in a certain period of time; "he clocked the runners") 2. (3) time -- (assign a time for an activity or event; "The candidate carefully timed his appearance at the disaster scene") 3. (1) time -- (set the speed, duration, or execution of; "we time the process to manufacture our cars very precisely") 4. time -- (regulate or set the time of; "time the clock") 5. time -- (adjust so that a force is applied and an action occurs at the desired time; "The good player times his swing so as to hit the ball squarely") --- WordNet end ---