Correlation Between Docetaxel Clearance and Estimated Cytochrome P450 Activity by Urinary Metabolite of Exogenous Cortisol

2000 ◽  
Vol 18 (11) ◽  
pp. 2301-2308 ◽  
Author(s):  
Noboru Yamamoto ◽  
Tomohide Tamura ◽  
Yoshikazu Kamiya ◽  
Ikuo Sekine ◽  
Hideo Kunitoh ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Practical Method ◽  
Interpatient Variability ◽  
Cyp3a4 Activity ◽  
Time Curve ◽  
Glycoprotein P ◽  
Cytochrome P450 Activity ◽  
Free Cortisol ◽  
Cyp3a4 Enzyme ◽  
The Individual

PURPOSE: There is no simple and practical method for the estimation of the interpatient variability of cytochrome P450 (CYP3A4) enzyme activity. Cortisol is metabolized by this enzyme and excreted as 6-beta-hydroxycortisol (6β-OHF) and free-cortisol (FC) in urine, and docetaxel is also metabolized by hepatic CYP3A4 enzyme. We developed a new method for the estimation of CYP3A4 activity by measuring urinary cortisol metabolite after administration of exogenous cortisol. This study was aimed at assessing the predictability of the individual activity of CYP3A4 estimated by this method. PATIENTS AND METHODS: Thirty patients with advanced non–small-cell lung cancer were entered onto this study. Hydrocortisone 300 mg was administered intravenously, and urinary 6β-OHF and FC were measured. More than 2 days later, 60 mg/m2 of docetaxel was administered intravenously with pharmacokinetic sampling. The correlation between docetaxel pharmacokinetics and estimated interpatient variability of CYP3A4 activity with the application of our method was assessed. RESULTS: After cortisol administration, the total amount of 24-hour urinary 6β-OHF (T6β-OHF) increased about 60-fold compared with pretreatment levels, averaging 12,273 ± 4,076 μg/d (mean ± SD). Docetaxel clearance (CL) and area under the concentration-time curve averaged 24.5 ± 6.4 L/h/m2 and 2.66 ± 0.91 mg/L 8729· h, respectively. An excellent correlation between docetaxel CL and T6β-OHF was observed (r = .867). In multivariate analysis, T6β-OHF (P < .001), alpha-1-acid glycoprotein (P < .004), AST (P = .007), and age (P = .022) significantly correlated with docetaxel CL. CONCLUSION: The interpatient variability of CYP3A4 activity and docetaxel CL could be predicted by measuring T6β-OHF after cortisol administration.

Randomized Pharmacokinetic and Pharmacodynamic Study of Docetaxel: Dosing Based on Body-Surface Area Compared With Individualized Dosing Based on Cytochrome P450 Activity Estimated Using a Urinary Metabolite of Exogenous Cortisol

2005 ◽  
Vol 23 (6) ◽  
pp. 1061-1069 ◽  
Author(s):  
Noboru Yamamoto ◽  
Tomohide Tamura ◽  
Haruyasu Murakami ◽  
Tatsu Shimoyama ◽  
Hiroshi Nokihara ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Urinary Metabolite ◽  
Interpatient Variability ◽  
Time Curve ◽  
Percentage Decrease ◽  
Cytochrome P450 Activity ◽  
Individualized Dosing

Purpose Docetaxel is metabolized by cytochrome P450 (CYP3A4) enzyme, and the area under the concentration-time curve (AUC) is correlated with neutropenia. We developed a novel method for estimating the interpatient variability of CYP3A4 activity by the urinary metabolite of exogenous cortisol (6-beta-hydroxycortisol [6-β-OHF]). This study was designed to assess whether the application of our method to individualized dosing could decrease pharmacokinetic (PK) and pharmacodynamic (PD) variability compared with body-surface area (BSA) –based dosing. Patients and Methods Fifty-nine patients with advanced non–small-cell lung cancer were randomly assigned to either the BSA-based arm or individualized arm. In the BSA-based arm, 60 mg/m2 of docetaxel was administered. In the individualized arm, individualized doses of docetaxel were calculated from the estimated clearance (estimated clearance = 31.177 + [7.655 × 10−4 × total 6-β-OHF] − [4.02 × alpha-1 acid glycoprotein] − [0.172 × AST] − [0.125 × age]) and the target AUC of 2.66 mg/L · h. Results In the individualized arm, individualized doses of docetaxel ranged from 37.4 to 76.4 mg/m2 (mean, 58.1 mg/m2). The mean AUC and standard deviation (SD) were 2.71 (range, 2.02 to 3.40 mg/L · h) and 0.40 mg/L · h in the BSA-based arm, and 2.64 (range, 2.15 to 3.07 mg/L · h) and 0.22 mg/L · h in the individualized arm, respectively. The SD of the AUC was significantly smaller in the individualized arm than in the BSA-based arm (P < .01). The percentage decrease in absolute neutrophil count (ANC) averaged 87.1% (range, 59.0 to 97.7%; SD, 8.7) in the BSA-based arm, and 87.4% (range, 78.0 to 97.2%; SD, 6.1) in the individualized arm, suggesting that the interpatient variability in percent decrease in ANC was slightly smaller in the individualized arm. Conclusion The individualized dosing method based on the total amount of urinary 6-β-OHF after cortisol administration can decrease PK variability of docetaxel.

Enhanced intrinsic CYP3A4 activity in human hepatic C3A cells with optically controlled CRISPR/dCas9 activator complex

2018 ◽  
Vol 10 (12) ◽  
pp. 780-790
Author(s):  
Shuo Han ◽  
Shiruo Wei ◽  
Xuan Wang ◽  
Xu Han ◽  
Mingzhi Zhang ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Bioartificial Liver ◽  
Liver Development ◽  
Cytochrome P450 3A4 ◽  
Cyp3a4 Activity ◽  
Cyp3a4 Enzyme ◽  
Activator Complex

Human hepatic C3A cells have been applied in bioartificial liver development, although these cells display low intrinsic cytochrome P450 3A4 (CYP3A4) enzyme activity.

scholarly journals Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis

2017 ◽  
Vol 45 (12) ◽  
pp. 1317-1325 ◽  
Author(s):  
Hui Li ◽  
Mark J. Canet ◽  
John D. Clarke ◽  
Dean Billheimer ◽  
Stavra A. Xanthakos ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Nonalcoholic Steatohepatitis ◽  
Cytochrome P450 Activity ◽  
P450 Activity

Modulation of Cytochrome P450 Activity by 18β-Glycyrrhetic Acid and its Consequence on Buspirone Pharmacokinetics in Rats

2015 ◽  
Vol 29 (8) ◽  
pp. 1188-1194 ◽  
Author(s):  
Sang-Bum Kim ◽  
Hyun-Jong Cho ◽  
Yeong Shik Kim ◽  
Dae-Duk Kim ◽  
In-Soo Yoon
Keyword(s):  
Cytochrome P450 ◽  
Glycyrrhetic Acid ◽  
Cytochrome P450 Activity ◽  
Pharmacokinetics In Rats ◽  
P450 Activity

scholarly journals Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects.

1997 ◽  
Vol 41 (10) ◽  
pp. 2196-2200 ◽  
Author(s):  
L J Lee ◽  
B Hafkin ◽  
I D Lee ◽  
J Hoh ◽  
R Dix
Keyword(s):  
Oral Dose ◽  
Healthy Subjects ◽  
High Fat ◽  
Time Curve ◽  
Mean Values ◽  
Treatment Groups ◽  
The Mean ◽  
The Individual ◽  
Individual Profiles ◽  
Fat Meal

The effects of food and sucralfate on the pharmacokinetics of levofloxacin following the administration of a single 500-mg oral dose were investigated in a randomized, three-way crossover study with young healthy subjects (12 males and 12 females). Levofloxacin was administered under three conditions: fasting, fed (immediately after a standardized high-fat breakfast), and fasting with sucralfate given 2 h following the administration of levofloxacin. The concentrations of levofloxacin in plasma and urine were determined by high-pressure liquid chromatography. By noncompartmental methods, the maximum concentration of drug in serum (Cmax), the time to Cmax (Tmax), the area under the concentration-time curve (AUC), half-life (t1/2), clearance (CL/F), renal clearance (CLR), and cumulative amount of levofloxacin in urine (Ae) were estimated. The individual profiles of the drug concentration in plasma showed little difference among the three treatments. The only consistent effect of the coadministration of levofloxacin with a high-fat meal for most subjects was that levofloxacin absorption was delayed and Cmax was slightly reduced (Tmax, 1.0 and 2.0 h for fasting and fed conditions, respectively [P = 0.002]; Cmax, 5.9 +/- 1.3 and 5.1 +/- 0.9 microg/ml [90% confidence interval = 0.79 to 0.94] for fasting and fed conditions, respectively). Sucralfate, which was administered 2 h after the administration of levofloxacin, appeared to have no effect on levofloxacin's disposition compared with that under the fasting condition. Mean values of Cmax and AUC from time zero to infinity were 6.7 +/- 3.2 microg/ml and 47.9 +/- 8.4 microg x h/ml, respectively, following the administration of sucralfate compared to values of 5.9 +/- 1.3 microg/ml and 50.5 +/- 8.1 microg x h/ml, respectively, under fasting conditions. The mean t1/2, CL/F, CLR, and Ae values were similar among all three treatment groups. In conclusion, the absorption of levofloxacin was slightly delayed by food, although the overall bioavailability of levofloxacin following a high-fat meal was not altered. Finally, sucralfate did not alter the disposition of levofloxacin when sucralfate was given 2 h after the administration of the antibacterial agent, thus preventing a potential drug-drug interaction.

scholarly journals Using Canopy Measurements to Predict Soybean Seed Yield

2021 ◽  
Vol 13 (16) ◽  
pp. 3260
Author(s):  
Peder K. Schmitz ◽  
Hans J. Kandel
Keyword(s):  
Seed Yield ◽  
Prediction Models ◽  
Plant Density ◽  
Soybean Seed ◽  
Canopy Cover ◽  
Growing Season ◽  
Practical Method ◽  
Coefficient Of Determination ◽  
Planting Dates ◽  
The Individual

Predicting soybean [Glycine max (L.) Merr.] seed yield is of interest for crop producers to make important agronomic and economic decisions. Evaluating the soybean canopy across a range of common agronomic practices, using canopy measurements, provides a large inference for soybean producers. The individual and synergistic relationships between fractional green canopy cover (FGCC), photosynthetically active radiation (PAR) interception, and a normalized difference vegetative index (NDVI) measurements taken throughout the growing season to predict soybean seed yield in North Dakota, USA, were investigated in 12 environments. Canopy measurements were evaluated across early and late planting dates, 407,000 and 457,000 seeds ha−1 seeding rates, 0.5 and 0.8 relative maturities, and 30.5 and 61 cm row spacings. The single best yield predictor was an NDVI measurement at R5 (beginning of seed development) with a coefficient of determination of 0.65 followed by an FGCC measurement at R5 (R2 = 0.52). Stepwise and Lasso multiple regression methods were used to select the best prediction models using the canopy measurements explaining 69% and 67% of the variation in yield, respectively. Including plant density, which can be easily measured by a producer, with an individual canopy measurement did not improve the explanation in yield. Using FGCC to estimate yield across the growing season explained a range of 49% to 56% of yield variation, and a single FGCC measurement at R5 (R2 = 0.52) being the most efficient and practical method for a soybean producer to estimate yield.

scholarly journals Hepatic Cytochrome P450 Activity, Abundance, and Expression Throughout Human Development

2016 ◽  
Vol 44 (7) ◽  
pp. 984-991 ◽  
Author(s):  
N. C. Sadler ◽  
P. Nandhikonda ◽  
B.-J. Webb-Robertson ◽  
C. Ansong ◽  
L. N. Anderson ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Development ◽  
Cytochrome P450 Activity ◽  
P450 Activity ◽  
Hepatic Cytochrome

Molecular imaging of cytochrome P450 activity in mice

2012 ◽  
Vol 65 (5) ◽  
pp. 531-536 ◽  
Author(s):  
Chiara Roncoroni ◽  
Nicoletta Rizzi ◽  
Electra Brunialti ◽  
James J. Cali ◽  
Dieter H. Klaubert ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Molecular Imaging ◽  
Cytochrome P450 Activity ◽  
P450 Activity
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