scholarly journals The Effect of Posaconazole and Isavuconazole on the Pharmacokinetics of Erdafitinib in Beagle Dogs by UPLC-MS/MS

2021 ◽  
Vol 12 ◽  
Author(s):  
Lan-hong Ruan ◽  
Ling-ling Fan ◽  
Kun Wang ◽  
Wan-qi Zhang ◽  
Xiao-jun Wang ◽  
...  
Keyword(s):  
Ultra Performance Liquid Chromatography ◽  
Self Control ◽  
Pharmacokinetic Parameters ◽  
Beagle Dogs ◽  
Limit Of Quantification ◽  
Dog Plasma ◽  
Liquid Chromatography Tandem Mass ◽  
Group A ◽  
Group B ◽  
Second Period

Objective: A robust, quick, and reliable ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for the quantification of erdafitinib in beagle dog plasma was developed and validated to evaluate the changes of posaconazole and isavuconazole on the pharmacokinetics of erdafitinib in beagle dogs, respectively.Methods: This experiment adopted a three-period self-control experimental design. In the first period (group A), erdafitinib was orally administered to six beagle dogs at a dose of 4 mg/kg. In the second period (group B), the same six beagle dogs were orally given posaconazole at a dose of 7 mg/kg, and after 30 min, erdafitinib was orally given. In the third period (group C), isavuconazole at a dose of 7 mg/kg was given orally, and then, erdafitinib was orally given. At the different time points after erdafitinib was given in the three periods, the blood samples were collected. The concentration of erdafitinib was detected by the developed UPLC-MS/MS method. DAS 2.0 was used to calculate the pharmacokinetic parameters of erdafitinib.Results: Erdafitinib had a good linear relationship in the range of 1–500 ng/ml, and the lower limit of quantification was 1 ng/ml. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. After erdafitinib was combined with posaconazole, the Cmax and AUC0→t of erdafitinib increased by 27.19% and 47.62%, respectively, and the t1/2 was prolonged to 6.33 h. After erdafitinib was combined with isavuconazole, the Cmax and AUC0→t of erdafitinib increased by 23.13% and 54.46%, respectively, and the t1/2 was prolonged to 6.31 h.Conclusion: A robust and reliable UPLC-MS/MS method was fully optimized and developed to detect the plasma concentration of erdafitinib in beagle dogs. Posaconazole and isaconazole could inhibit the metabolism of erdafitinib in beagle dogs and increase the plasma exposure of erdafitinib.

scholarly journals Effect of Sijunzi Pills on Pharmacokinetics of Omeprazole in Beagle Dogs by HPLC-UV: A Herb-Drug Interaction Study

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Hua-ling Xia ◽  
Xin-jie Zhao ◽  
Yu-ji Zhang ◽  
Xiao-hang Su ◽  
Bo Sun ◽  
...  
Keyword(s):  
Internal Standard ◽  
Hplc Method ◽  
Array Detector ◽  
Pharmacokinetic Parameters ◽  
Beagle Dogs ◽  
Beagle Dog ◽  
Dog Plasma ◽  
Group A ◽  
Group B

A sensitive high-performance liquid chromatography (HPLC-UV) method for determination of omeprazole in beagle dog plasma was developed and to investigate the effect of Sijunzi pills (SJZPs) on the pharmacokinetics of omeprazole in beagle dogs. The beagle dog plasma was extracted with ethyl acetate and n-hexane under alkaline conditions. Omeprazole and internal standard (IS, fluconazole) were separated on an XDB-C18 column, and acetonitrile and 0.1% trifluoroacetic acid were used as the mobile phase. Omeprazole and IS were detected by using a diode array detector. This experiment adopts the experimental design of double-cycle self-control. In the first cycle (group A), six beagle dogs were given omeprazole 0.67 mg/kg orally in a single dose. In the second period (group B), the same six beagle dogs were orally given SJZPs 0.2 g/kg twice a day for 7 consecutive days, and then, omeprazole was orally given. At the different time points after omeprazole was given in the two periods, the blood samples were collected. The concentration of omeprazole was detected by the developed HPLC method. DAS 2.0 was used to calculate the pharmacokinetic parameters of omeprazole. Under the current experimental conditions, this UPLC method showed good linearity in the detection of omeprazole. Interday and intraday precision did not exceed 10%, and the range of accuracy values were from −1.43% to 2.76%. The results of extraction recovery and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The Cmax of omeprazole in group B was 61.55% higher than that in group A, and the AUC(0−t) and AUC(0−∞) of omeprazole in group B were 63.96% and 63.65% higher those that in group A, respectively. At the same time, the clearance (CL) and apparent volume of distribution (Vd) decreased in group B. In this study, an HPLC method for the determination of plasma omeprazole concentration was established. SJZPs could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. It is suggested that when SJZPs are combined with omeprazole, attention should be paid to the herb-drug interactions and possible adverse reactions.

scholarly journals Quantitation of Apremilast in Beagle Dogs Plasma by UPLC-MS-MS and Its Application to Pharmacokinetic Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wei Xiong ◽  
Ling Wang ◽  
Haiyan Zhang ◽  
Xiaoqiu Tao ◽  
Xuehua Jiang ◽  
...  
Keyword(s):  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Ammonium Formate ◽  
Pharmacokinetic Studies ◽  
Beagle Dogs ◽  
Beagle Dog ◽  
Dog Plasma ◽  
Liquid Chromatography Tandem Mass

A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of apremilast in beagle dog plasma has been developed and successfully validated in the current study. Clopidogrel was employed as an internal standard (IS), and liquid-liquid extraction by tert-butylmethyl ether was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH Shield RP18 column (50 mm × 2.1 mm, 1.7 μm) with 5 mM ammonium formate water and 5 mM ammonium formate methanol as the mobile phase with gradient elution. Calibration plots were linear in the range of 2–3000 ng/mL for apremilast in beagle dog plasma. Mean recoveries of apremilast in beagle dogs plasma ranged from 87.4% to 97.4%. The intrarun and interrun precision was less than 6% and 9%, respectively, with the accuracy between 92.4% and 101.1%. The method has also been successfully applied in the pharmacokinetics study of apremilast. The mean t1/2Z was 5.41 h for 30 mg·day−1 for beagle dogs after oral administration. The AUC0-t increased linearly from 3.51 to 1802.13  μ g   L − 1 ∗ h after administration of single doses.

Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Vichit Supornsilchai ◽  
Chutima Jantarat ◽  
Wichit Nosoognoen ◽  
Sopon Pornkunwilai ◽  
Suttipong Wacharasindhu ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Estrogenic Activity ◽  
Age At Onset ◽  
Ultra Performance Liquid Chromatography ◽  
Cross Sectional Study ◽  
Normal Weight ◽  
Control Groups ◽  
Limit Of Quantification ◽  
Cross Sectional ◽  
Liquid Chromatography Tandem Mass

AbstractReports on the secular trend of pubertal onset indicate a recent earlier start especially in girls. Bisphenol A (BPA), which posses estrogenic activity, might be a cause of advanced puberty. The objective of the study was to determine the association between BPA and advanced puberty.A cross-sectional study was conducted in patients with advanced puberty (n=41) compared to age-matched controls (n=47). Anthropometric measurements, estradiol, basal and gonadotropin releasing hormone (GnRH)-stimulated follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, uterine sizes, ovarian diameters and bone ages were obtained. Urinary BPA concentrations were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MSMS) with the lower limit of quantification (LLOQ) of 0.05 ng/mL.The median adjust-BPA concentration in advanced puberty group was higher than in control groups [1.44 vs. 0.59 μg/g creatinine (Cr): p<0.05]. We also found that the median adjust-BPA concentration in girls with advanced puberty who were overweight/obese, was greater than in the normal pubertal overweight/obese girls (1.74 vs. 0.59 μg/g Cr: p<0.05), and was in the same trend among normal weight girls with advanced and normal puberty (0.83 vs. 0.49 μg/g Cr: p=0.09), but not statistically significant.The present findings suggest that BPA exposure appears to be related to an earlier age at onset of puberty especially in obese girls.

Carbamazepine Phakmacokinetics in Obese and Lean Subjects

1995 ◽  
Vol 29 (9) ◽  
pp. 843-847 ◽  
Author(s):  
Yoseph Caraco ◽  
Ester Zylber-Katz ◽  
Elliot M Berry ◽  
Micha Levy
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Ideal Body Weight ◽  
Obese Group ◽  
University Hospital ◽  
Pharmacokinetic Parameters ◽  
Group A ◽  
Obese Subjects ◽  
Group B ◽  
Lean Group

Objective: To compare carbamazepine pharmacokinetic parameters between obese and lean subjects following the administration of a single 200-mg tablet. Design: Single-dose intervention, open study. Setting: Teaching university hospital. Subjects: Eighteen obese (group A) otherwise healthy subjects, referred to the metabolic outpatient clinic, and 13 healthy lean (group B) volunteers. Inclusion criterion for the obese subjects was a body mass index (BMI = weight/height2) of more than 30 kg/m2. In the obese group, mean ± SD total body weight (TBW), BMI, and percent of ideal body weight (IBW) were 111.4 ± 19.9 kg, 38.8 ± 6.0 kg/m2, and 182.7% ± 30.7%, respectively. These values were significantly greater than the respective values of 63.2 ± 8.3 kg, 22.4 ± 1.6 kg/m2, and 105.8% ± 5.8% obtained in the lean group (p < 0.001). Intervention: Single-dose oral administration of carbamazepine 200-mg tablet (Teril, Taro, Israel). Outcomes: Carbamazepine elimination half-life (t1/2), apparent volume of distribution (Varea/F), and its oral clearance (Clpo/F) were derived from the drug concentration-time curves. Results: Carbamazepine Varea/F and t1/2 were significantly greater in group A than in group B (98.4 ± 26.9 vs. 60.7 ± 8.5 L, respectively, p < 0.001; and 59.4 ± 14.7 vs. 31.0 ± 5.0 h, respectively, p < 0.001), but its Clpo/F was reduced only slightly in obese as compared with lean subjects (19.8 ± 5.2 vs. 23.0 ± 4.6 mL/min, respectively, p = 0.07). Correction for IBW yielded similar results for Varea/F and t1/2, but Clpo/F per kg of IBW was significantly smaller in the obese than in the lean subjects (0.32 ± 0.07 vs. 0.39 ± 0.06 mL/min/kg of IBW, respectively, p < 0.02). Linear correlations were observed between Varea/F and TBW for both group A (r = 0.92, p < 0.001) and group B (r = 0.77, p < 0.002). Conclusions: In comparison with lean subjects, carbamazepine Varea/F is significantly greater in obese subjects and its t1/2 is markedly prolonged. The minor nonsignificant effect of obesity on carbamazepine Clpo/F suggests that in obese subjects the carbamazepine daily dose should be based on IBW, not on TBW.

scholarly journals Artemisinin Pharmacokinetics and Efficacy in Uncomplicated-Malaria Patients Treated with Two Different Dosage Regimens

2002 ◽  
Vol 46 (4) ◽  
pp. 1026-1031 ◽  
Author(s):  
Toufigh Gordi ◽  
Dinh Xuan Huong ◽  
Trinh Ngoc Hai ◽  
Nguyen Thi Nieu ◽  
Michael Ashton
Keyword(s):  
High Performance ◽  
Parasite Clearance ◽  
Oral Dosage ◽  
Pharmacokinetic Parameters ◽  
Oral Clearance ◽  
Dosage Regimens ◽  
Drug Concentrations ◽  
Group A ◽  
Group B ◽  
Pass Metabolism

ABSTRACT The immediate efficacies of two oral dosage regimens of artemisinin were investigated in 77 male and female adult Vietnamese falciparum malaria patients randomly assigned to treatment with either 500 mg of artemisinin daily for 5 days (group A; n = 40) or artemisinin at a dose of 100 mg per day for 2 days, with the dose increased to 250 mg per day for 2 consecutive days and with a final dose of 500 mg on the fifth day (group B; n = 37). Parasitemia was monitored every 4 h. The average parasite clearance time was longer in group B than in group A (means ± standard deviations, 50 ± 23 and 34 ± 14 h, respectively; P < 0.01). Artemisinin concentrations in saliva samples obtained on days 1 and 5 were quantified by high-performance liquid chromatography. The average oral clearance, based on saliva drug concentrations in group B patients, was twofold higher than that in group A patients on day 1 (P < 0.01), with no differences in drug half-lives (P = 0.40), indicating a saturable first-pass metabolism. Female patients had higher oral clearance values on day 1. Artemisinin's pharmacokinetic parameters were similar on day 5 in both groups, although a significant increase in oral clearance from day 1 to day 5 was evident. Thus, artemisinin exhibited both dose- and time-dependent pharmacokinetics. The escalating dose studied did not result in higher artemisinin concentrations toward the end of the treatment period.

scholarly journals Cocktail Method: Effect of the Bletilla striata Extracts on CytochromeP450 Activity in Rat

2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110324
Author(s):  
Yong Huang ◽  
Zu-Ying Zhou ◽  
Zi-Peng Gong ◽  
Yue-Ting Li ◽  
Si-Ying Chen ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Side Effects ◽  
Ultra Performance Liquid Chromatography ◽  
Pharmacokinetic Parameters ◽  
Tandem Mass ◽  
Control Groups ◽  
Bletilla Striata ◽  
Method Effect ◽  
Liquid Chromatography Tandem Mass ◽  
Different Doses

Bletilla striata is a dried tuber of B striata (Thunb.) Reichb.f. of Orchidaceae plant, which is mainly used for hemoptysis, vomiting blood, trauma bleeding, sore swollen poison, and cracked skin. There have been few research reports on the effect of this herb on cytochrome P450 (CYP), therefore, the study was aimed to investigate the effects of the B striata extracts on the activity of 6 subtypes (CYP2D6, 1A2, 2C19, 2E1, 3A4, and 2C9) using a cocktail method. The B striata extracts were administrated to rats in 0.21 or 0.63 g/kg once a day for 7 or 14 days. The 3 control groups were used to ensure the accuracy of the results. Subsequently, a cocktail of tolbutamide, chlorzoxazone, midazolam, metoprolol, omeprazole, and caffeine was injected. A ultra performance liquid chromatography–tandem mass spectrometer was developed and validated to investigate the concentration of the probes and the pharmacokinetic parameters were calculated to investigate the effects of the extracts on the activity of 6 enzymes under different doses and different dosing periods. The results suggested that the B striata extracts could induce the activities of CYP2D6, 1A2, and 2C19 and could inhibit the activities of CYP2E1, 3A4, and 2C9. When used in combination with drugs that are metabolized by CYP2D6, 1A2, 2C19, 2E1, 3A4, and 2C9, appropriate dose adjustments were needed to avoid toxic side effects caused by drug interactions.

scholarly journals Determination of myrislignan levels in BALB/c mouse plasma by LC-MS/MS and a comparison of its pharmacokinetics after oral and intraperitoneal administration

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jili Zhang ◽  
Hongfei Si ◽  
Jichao Sun ◽  
Kun Lv ◽  
Biqing Yan ◽  
...  
Keyword(s):  
Formic Acid ◽  
Intraperitoneal Administration ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Clinical Effects ◽  
Limit Of Quantification ◽  
Mouse Plasma ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Abstract Background Myrislignan is a natural product from Myristica sp. with diverse pharmacological activities. Recently, the anti-Toxoplasma gondii (T. gondii) activity of myrislignan has been proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effects of myrislignan. Results In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify myrislignan levels in mouse plasma using dehydrodiisoeugenol as an internal standard (IS) in positive ion mode. Chromatographic separation of the analytes was achieved using an ACE Ultracore Super C18 analytical column (2.5 μm, 2.1 × 50 mm) at 30 °C. A gradient mobile phase consisting of water (0.1 % formic acid) and acetonitrile (0.1 % formic acid) was delivered at a flow rate of 0.4 mL/min. Myrislignan and the IS eluted at 1.42 and 1.71 min, respectively. A good excellent linear response across the concentration range of 1-1000 ng/mL was achieved (r2 = 0.9973). The lower limit of quantification (LLOQ) was 1 ng/mL, and the inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) less than 10 %. The method was applied to examine the pharmacokinetics of myrislignan in mouse plasma following a single oral administration of 200 mg/kg or intraperitoneal administration of 50 mg/kg myrislignan, and the bioavailability (F) of orally administered myrislignan was only 1.97 % of the bioavailability of intraperitoneally administered myrislignan. Conclusions A rapid and sensitive LC-MS/MS method has been was developed, validated and successfully used to determine myrislignan levels in mice after oral or intraperitoneal administration. This study is the first to report the pharmacokinetic parameters of myrislignan in mice and to compare its pharmacokinetics after oral and intraperitoneal administration, which will be useful for further research on the administration of myrislignan in animals and humans.

scholarly journals Simultaneous Quantification of Five Flavanone Glycosides in Rat Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Comparative Pharmacokinetic Study of Aurantii Fructus Immaturus and Aurantii Fructus Extracts

2019 ◽  
Vol 102 (3) ◽  
pp. 781-787 ◽  
Author(s):  
Pei Li ◽  
Su-Ling Zeng ◽  
Zi-Yuan Wang ◽  
Qiang Yin ◽  
Zhi-Ming Bi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Pharmacokinetic Study ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Tandem Mass ◽  
Liquid Chromatography Tandem Mass ◽  
Health Promoting

Abstract Background: Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are two traditional citrus herbs with health-promoting and nutritive properties. Objective: This paper presents the first attempt to simultaneously investigate the absorption of five major flavanone glycosides, namely narirutin, naringin, hesperidin, neohesperidin, and poncirin, in rat plasma following a single oral administration of AFI and AF extracts to rats. Methods: The plasma concentrations were determined by liquid–liquid extraction followed by a rapid and sensitive ultra-performance LC-tandem mass spectrometry method. Pharmacokinetic parameters were analyzed by noncompartmental modeling using DAS software. Results: The developed method was validated and successfully applied to the pharmacokinetic study of these five flavanone glycosides. Conclusions: The comparison of the pharmacokinetic parameters of flavanone glycosides showed that the absorption of AF extract was lower, while the elimination was relatively rapid, compared with those of AFI extract. Highlights: This study may be useful for further utilization of these two citrus herbs.

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