scholarly journals Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4276
Author(s):  
Li Ping ◽  
Bingyong Xu ◽  
Qian Zhou ◽  
Yawen Hong ◽  
Qingmei Sun ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Dependent Manner ◽  
Adult Rats ◽  
Time Curve ◽  
Juvenile Rats ◽  
Potential Safety ◽  
Final Time Point

Forchlorfenuron (CPPU) is a plant growth regulator extensively used in agriculture. However, studies on CPPU pharmacokinetics are lacking. We established and validated a rapid, sensitive, and accurate liquid chromatography–mass spectrometry method for CPPU detection in rat plasma. CPPU pharmacokinetics was evaluated in adult and juvenile rats orally treated with 10, 30, and 90 mg/kg of the compound. The area under the plasma drug concentration–time curve from 0 to 24 h (AUC), at the final time point sampled (AUC0–t), and the maximum drug concentration of CPPU increased in a dose-dependent manner. The pharmacokinetic parameters AUC0–t and absolute bioavailability were higher in the juvenile rats than in adult rats. The mean residence time and AUC0–t of juvenile rats in the gavage groups, except for the 10 mg/kg dose, were significantly higher in comparison to those observed for adult rats (p < 0.001). The plasma clearance of CPPU in juvenile rats was slightly lower than that in the adult rats. Taken together, juvenile rats were more sensitive to CPPU than adult rats, which indicates potential safety risks of CPPU in minors.

scholarly journals Predicting the Outcome of Voriconazole Individualized Medication Using Integrated Pharmacokinetic/Pharmacodynamic Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Ping Yang ◽  
Wei Liu ◽  
Jiajia Zheng ◽  
Yuanyuan Zhang ◽  
Li Yang ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Minimal Inhibitory Concentration ◽  
Logistic Regression Analysis ◽  
Drug Concentration ◽  
Inhibitory Concentration ◽  
Free Drug ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time

Therapeutic drug monitoring is considered to be an effective tool for the individualized use of voriconazole. However, drug concentration measurement alone doesn’t take into account the susceptibility of the infecting microorganisms to the drug. Linking pharmacodynamic data with the pharmacokinetic profile of individuals is expected to be an effective method to predict the probability of a certain therapeutic outcome. The objective of this study was to individualize voriconazole regimens by integrating individual pharmacokinetic parameters and pathogen susceptibility data through Monte Carlo simulations The individual pharmacokinetic parameters of 35 hospitalized patients who received voriconazole were calculated based on a validated population pharmacokinetic model. The area under the concentration-time curve for free drug/minimal inhibitory concentration (fAUCss/MIC) &gt; 25 was selected as the pharmacokinetic/pharmacodynamic (PK/PD) parameter predicting the efficacy of voriconazole. The cumulative fraction of response (CFR) of the target value was assessed. To verify this conclusion, a logistic regression analysis was used to explore the relationship between actual clinical efficiency and the CFR value. For the 35 patients, the area under the free drug concentration-time curve (fAUCss) was calculated to be 34.90 ± 21.67 mgh/L. According to the dualistic logistic regression analysis, the minimal inhibitory concentration (MIC) value of different kinds of fungi had a great influence on the effectiveness of clinical treatment. It also showed that the actual clinical efficacy and the CFR value of fAUCss/MIC had a high degree of consistency. The results suggest that it is feasible to individualize voriconazole dosing and predict clinical outcomes through the integration of data on pharmacokinetics and antifungal susceptibility.

scholarly journals Pharmacokinetic UPLC–MS/MS studies on byakangelicol after oral and intravenous administration to rats

2020 ◽  
Vol 32 (1) ◽  
pp. 49-52
Author(s):  
Xi Bao ◽  
Bingge Huang ◽  
Yiting Mao ◽  
Zhiguang Zhang ◽  
Yunfang Zhou ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Multiple Reaction Monitoring ◽  
A549 Cells ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Dependent Manner ◽  
Limit Of Quantitation ◽  
Intravenous And Oral Administration

Byakangelicol is one of coumarins from Baizhi and has been shown to inhibit the release of PGE2 from human lung epithelial A549 cells in a dose-dependent manner. A sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and full validated for the quantification of byakangelicol in rat plasma. The pharmacokinetics of byakangelicol after both intravenous (5 mg/kg) and oral (15 mg/kg) administrations were studied. Chromatographic separation was performed on an ultra-performance liquid chromatography ethylene bridged hybrid (UPLC BEH) C18 column with acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min; fargesin was used as the internal standard (IS). The following quantitative analysis of byakangelicol was utilized in the multiple reaction monitoring mode. The samples were extracted from rat plasma via protein precipitation using acetonitrile. In the concentration range of 1–2000 ng/mL, the method correlated linearity (r > 0.995) with a lower limit of quantitation (LLOQ) of 1 ng/mL. Intra-day precision was less than 11%, and inter-day precision was less than 12%. The accuracy was between 92.0% and 108.7%, the recovery was better than 89.6%, and the matrix effect was between 85.9% and 98.6%. The method was successfully applied to a pharmacokinetic study of byakangelicol after intravenous and oral administration, and the absolute bioavailability was 3.6%.

Local Vancomycin Concentrations after Intra-articular Injection into the Knee Joint: An Experimental Porcine Study

2019 ◽  
Author(s):  
Mats Bue ◽  
Maja B. Thomassen ◽  
Ole H. Larsen ◽  
Andrea R. Jørgensen ◽  
Maiken Stilling ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Knee Joint ◽  
Drug Concentration ◽  
Subcutaneous Tissue ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Systemic Circulation ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Prosthetic Joint Infections

AbstractIntra-articular injection of vancomycin may be an important antimicrobial prophylactic supplement to systemic administration in the prevention of prosthetic joint infections. In eight female pigs, 500 mg of diluted vancomycin was given by intra-articular injection into the knee joint. Microdialysis was used for dense sampling of vancomycin concentrations over 12 hours in the synovial fluid of the knee joint, and in the adjacent femoral and tibial cancellous bone and subcutaneous tissue. Venous blood samples were obtained as reference. The mean (standard deviation [SD]) peak drug concentration of vancomycin in the synovial fluid of the knee joint was 5,277 (5,668) μg/mL. Only one pig failed to reach a peak drug concentration above 1,000 μg/mL. The concentration remained high throughout the sampling interval with a mean (SD) concentration of 337 (259) μg/mL after 690 minutes. For all extraarticular compartments, the pharmacokinetic parameters (area under the concentration time-curve, peak drug concentration, and time to peak drug concentration) were comparable. The highest extraarticular mean (SD) peak drug concentration of 4.4 (2.3) μg/mL was found in subcutaneous tissue. An intra-articular injection of 500 mg diluted vancomycin was found to provide significant prophylactic mean concentrations for at least 12 hours in the synovial fluid of the knee joint. Correspondingly, the adjacent tissue and plasma concentrations were low but remained stable, signifying low risk of systemic toxic side effects and a slow release or uptake from the synovium to the systemic circulation.

scholarly journals The LC-MS/MS-Based Measurement of Isopimaric Acid in Rat Plasma and Application of Pharmacokinetics

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Doudou Huang ◽  
Jiaxi Cheng ◽  
Junqin Mao ◽  
Senlin Ma ◽  
Zenan Du ◽  
...  
Keyword(s):  
Internal Standard ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Isopimaric Acid ◽  
Clinical Utilization ◽  
Mechanistic Basis ◽  
Oral Doses

Isopimaric acid (IPA) exhibits a diverse array of pharmacological activities, having been shown to function as an antihypertensive, antitumor, antibacterial, and hypocholesterolemic agent. However, few studies of the pharmacokinetics of IPA have been performed to date, and such analyses are essential to explore the in vivo mechanisms governing the biological activity of this compound. As such, we herein designed a selective LC-MS approach capable of quantifying serum IPA levels in model rats using an Agilent HC-C18 column ( 250   mm × 4.6   mm , 5 μm) via isocratic elution with a mobile phase composed of methanol 0.5% formic acid (91 : 9, v/v) at a 1 mL/min flow rate. Ion monitoring at m/z 301.2 [M-H]- was used to quantify IPA levels in plasma samples from these rats, while internal standard (IS) levels were assessed at m/z 455.3 [M-H]-. After validation, this approach was employed to conduct a pharmacokinetic analysis of rats administered IPA via the oral (p.o. 50, 100, or 200 mg/kg) and intravenous (i.v. 5 mg/kg) routes. Analyses of noncompartmental pharmacokinetic parameters revealed that IPA underwent secondary absorption following oral administration to these animals, with the two tested oral doses (50 and 100 mg/kg) being associated with respective absolute bioavailability values of 11.9% and 17.5%. In summary, this study may provide a foundation for future efforts to explore the mechanistic basis for the pharmacological activity of IPA, offering insights to guide its subsequent clinical utilization.

scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PENTOXIFYLLINE USING NATURAL MUCOADHESIVE POLYMERS

2019 ◽  
pp. 153-157
Author(s):  
GNANASEKARAN JOHN SELVARAJ ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Drug Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Fold Increase ◽  
Ocimum Basilicum ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Time Curve ◽  
Significant Difference

Objective: The present study was aimed to alter the pharmacokinetic parameters of the drug pentoxifylline using a novel natural mucoadhesive polymer from two different plants, Manilkara zapotta Linn and Ocimum basilicum Linn. Methods: The polymer was isolated and six batches of mucoadhesive tablets of pentoxifylline was formulated with 3 different concentrations of each polymer. The best formulation from each of the polymer was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as such as Cmax, tmax, AUC, AUMC, λz, t1/2, and MRT were determined. Results: The plasma drug concentration vs time curve shows the extended-release of pentoxifylline when compared with the conventional marketed formulation. The results show that there is no change in the peak plasma concentration, but the significant difference was observed in t½, which showed approximately 2.5 fold increase from 2.44 to 6.87 h and the AUC showed five-fold increase from 22.40 to 117.19 μg*h/ml, and other pharmacokinetic parameters, when compared with the marketed formulation. Conclusion: The isolated polymer from the plants Manilkara zapotta Linn. and Ocimum basilicum Linn can be used as a carrier for developing mucoadhesive formulations and it alter the pharmacokinetic of pentoxifylline positively.

scholarly journals A Single- and Multiple-Dose Study to Characterize the Pharmacokinetics, Safety, and Tolerability of Imipenem and Relebactam in Healthy Chinese Participants

2020 ◽  
Author(s):  
Xiaohong Wang ◽  
Na Liu ◽  
Yudong Wei ◽  
Shuang Zhang ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Adverse Events ◽  
Geometric Mean ◽  
Safety Data ◽  
Chinese Patients ◽  
Pharmacokinetic Parameters ◽  
Dependent Manner ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Multiple Doses ◽  
Healthy Chinese

Relebactam/imipenem/cilastatin is approved in the US to treat complicated urinary tract and intra-abdominal infections in patients that have limited or no alternative treatment options and HABP/VABP. Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian participants. This study evaluated pharmacokinetics, safety, and tolerability of relebactam/imipenem/cilastatin in 12 healthy Chinese participants after three single doses of increasing concentration (relebactam 125, 250, or 500 mg/cilastatin 250, 500, or 1000 mg/imipenem 250, 500, or 1000 mg) and after multiple doses every 6 h of a single concentration (relebactam 250 mg/cilastatin 500 mg/imipenem 500 mg) for 14 days. After single doses, area under the concentration–time curve (AUC) extrapolated to infinity (relebactam, 15.0–70.7 h*mg/liter; imipenem, 24.1–109.8 h*mg/liter; cilastatin, 18.4–95.3 h*mg/liter) and AUC from 0–6 h (relebactam, 14.2–66.3 h*mg/liter; imipenem, 23.4–107.3 h*mg/liter; cilastatin, 18.3–94.4 h*mg/liter) increased in a dose-dependent manner; clearance (relebactam, 6.9–8.3 liters/h; imipenem, 8.6–10.4 liters/h; cilastatin, 10.5–13.6 liters/h) and half-life (relebactam, 1.4–1.6 h; imipenem, 1.0–1.2 h; cilastatin, 0.7–1.0 h) were consistent between doses. Pharmacokinetic parameters after multiple doses were similar to parameters after a single dose (geometric mean ratios of 0.8–1.0 for all three agents). Relebactam/imipenem/cilastatin was well tolerated; mild adverse events occurred during single dosing, and one participant experienced serious adverse events after multiple doses. Pharmacokinetics and safety data are comparable with data from participants of other ethnicities, supporting the use of relebactam/imipenem/cilastatin at the approved dose and schedule in Chinese patients.

scholarly journals Pharmacokinetic parameters and optimal dosage of a florfenicol and tylosin mixture in beagle dogs

2018 ◽  
Vol 63 (No. 7) ◽  
pp. 329-334
Author(s):  
AF Mechesso ◽  
SJ Lee ◽  
NH Park ◽  
SC Park
Keyword(s):  
Antibacterial Activity ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Dilution Method ◽  
Optimal Dosage ◽  
Serum Concentrations ◽  
Beagle Dogs ◽  
Serum Samples ◽  
Time Curve ◽  
Minimum Inhibitory Concentrations

The aims of this study were to evaluate the in vitro antibacterial activity of a florfenicol and tylosin mixture and to determine the pharmacokinetic parameters of each drug following administration of the 2 : 1 florfenicol and tylosin mixture in beagle dogs. The antibacterial activity of the two antibiotics, both singly and as a mixture, was investigated in bacteria isolated from 119 beagle dogs. Minimum inhibitory concentrations were determined using the broth dilution method, whereas the checkerboard assay was used to evaluate the antibacterial effects of the combination of florfenicol and tylosin. The pharmacokinetic parameters of the two antibiotics were determined following administration of the mixture in beagle dogs. Serum concentrations of both drugs were analysed using high-performance liquid chromatography. Pharmacokinetics parameters such as area under the concentration-time curve, absolute bioavailability and systemic clearance were determined using non-compartmental analysis. The results showed that tylosin and florfenicol exerted varying degrees of antibacterial activity against the tested isolates. The combination of florfenicol and tylosin produced a synergistic and additive antibacterial effect. Analysis of the serum samples revealed a rapid and almost complete absorption of florfenicol and tylosin with mean bioavailabilities of 92.7% and 106.1%, respectively. The times needed to reach maximum concentration for florfenicol and tylosin were 1.5 and 3 h, respectively. Moreover, intramuscular injection of the mixture to beagle dogs resulted in serum concentrations that were higher than the corresponding minimum inhibitory concentrations in beagle dogs. This is the first study to report optimisation of florfenicol and tylosin doses following administration of a combination of the two drugs to beagle dogs.

scholarly journals Pharmacokinetics of Tildipirosin in Healthy and Mycoplasma gallisepticum Infected Chickens

2021 ◽  
Vol 10 (2) ◽  
pp. 119-123
Keyword(s):  
Mycoplasma Gallisepticum ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Group Iii ◽  
Concentration Time ◽  
Group I ◽  
Pharmacodynamic Profile ◽  
Plasma Concentration Time Curve ◽  
Insight Into

The pharmacokinetic features of tildipirosin were explored following a single dose of 4 mg/kg in healthy and Mycoplasma gallisepticum (M. gallisepticum) infected chickens. Eighteen healthy chickens (400-500g) were allocated into 3 groups (n=6); group I and II were received tildipirosin by intravenous (IV) and intramuscular (IM) routes, respectively. Group III was experimentally infected with M. gallisepticum and injected IM with tildipirosin after confirming the infection (9-10 days after inoculation of M. gallisepticum). Plasma samples were harvested at different time points until 14 days after tildipirosin injection to measure its concentrations using HPLC. After IM administration of tildipirosin in healthy chickens, the maximum concentration in plasma (Cmax), time to achieve Cmax (Tmax), area under the plasma concentration time curve from 0 to last time (AUC0-last), clearance (Cl-F-obs) and the absolute bioavailability were recorded to be 403.76ng/ml, 0.25 hr, 6.82 µg.hr/ml, 0.56L/hr/kg, and 103.50% respectively. Cmax and AUC0-last, were significantly lower in infected than healthy chickens, while Cl-F-obs was significantly higher in infected than healthy chickens. Therefore, M. gallispeticum infection produced significant changes in some of the pharmacokinetic parameters of tildipirosin in chickens. Further studies are warranted to assess pharmacokinetic/ pharmacodynamic profile of tildipirosin against M. gallisepticum in chickens and to gain deeper insight into its safety utilization in chickens.

scholarly journals Oral bioavailability and pharmacokinetics of ciprofloxacin in patients with AIDS.

1997 ◽  
Vol 41 (7) ◽  
pp. 1508-1511 ◽  
Author(s):  
R C Owens ◽  
K B Patel ◽  
M A Banevicius ◽  
R Quintiliani ◽  
C H Nightingale ◽  
...  
Keyword(s):  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Crossover Fashion ◽  
Time Curve ◽  
Mean Values ◽  
Severe Diarrhea ◽  
Concentration Time ◽  
Infectious Gastroenteritis ◽  
Dosing Regimens ◽  
The Mean

Few reports on the effects of AIDS on the absorption of orally (p.o.) administered agents exist. To help fill this informational gap, we administered ciprofloxacin to 12 patients with AIDS by two dosing regimens (400 mg given intravenously [i.v.] and 500 mg given p.o. every 12 h) in a randomized, crossover fashion. Pharmacokinetic parameters were determined by noncompartmental methods. Mean values (+/- standard deviations [SD]) for p.o. ciprofloxacin were as follows: peak concentration of drug in serum (Cmax), 2.94 +/- 0.51 microg/ml; time to Cmax, 1.38 +/- 0.43 h; area under the concentration-time curve from 0 to 12 h (AUC(0-12)), 12.13 +/- 3.21 microg x h/ml; and half-life (t(1/2)), 3.86 +/- 0.48 h. Mean values (+/- SD) for i.v. ciprofloxacin were as follows: Cmax, 3.61 +/- 0.82 microg/ml; time to Cmax, 1.0 h; AUC(0-12), 11.92 +/- 2.92 microg x h/ml; and t(1/2), 3.98 +/- 0.94 h. The mean percent absolute bioavailability for ciprofloxacin was calculated to be 82% +/- 13%, similar to the value for healthy volunteers. We conclude that ciprofloxacin when administered p.o. to patients with AIDS is well absorbed, as evidenced by excellent bioavailability and is not affected by gastrointestinal changes in the absence of infectious gastroenteritis and severe diarrhea.

scholarly journals A UPLC-ESI-MS/MS Method for Simultaneous Quantitation of Chlorogenic Acid, Scutellarin, and Scutellarein in Rat Plasma: Application to a Comparative Pharmacokinetic Study in Sham-Operated and MCAO Rats after Oral Administration of Erigeron breviscapus Extract

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1808 ◽  
Author(s):  
Siying Chen ◽  
Mei Li ◽  
Yueting Li ◽  
Hejia Hu ◽  
Ying Li ◽  
...  
Keyword(s):  
Oral Administration ◽  
Chlorogenic Acid ◽  
Drug Concentration ◽  
Limit Of Detection ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Time Points ◽  
Esi Ms ◽  
Erigeron Breviscapus

Erigeron breviscapus, a traditional Chinese medicine, is clinically used for the treatment of occlusive cerebral vascular diseases. We developed a sensitive and reliable ultra-performance liquid chromatography-electrospray-tandem mass spectrometry (UPLC-ESI-MS/MS) method for simultaneous quantitation of chlorogenic acid, scutellarin, and scutellarein, the main active constituents in Erigeron breviscapus, and compared the pharmacokinetics of these active ingredients in sham-operated and middle cerebral artery occlusion (MCAO) rats orally administrated with Erigeron breviscapus extract. Plasma samples were collected at 15 time points after oral administration of the Erigeron breviscapus extract. The levels of chlorogenic acid, scutellarin, and scutellarein in rat plasma at various time points were determined by a UPLC-ESI-MS/MS method, and the drug concentration versus time plots were constructed to estimate pharmacokinetic parameters. The concentration of chlorogenic acid in the plasma reached the maximum plasma drug concentration in about 15 min and was below the limit of detection after 4 h. Scutellarin and scutellarein showed the phenomenon of multiple absorption peaks in sham-operated and MCAO rats, respectively. Compared with the sham-operated rats, the terminal elimination half-life of scutellarein in the MCAO rats was prolonged by more than two times and the area under the curve of each component in the MCAO rats was significantly increased. The results showed chlorogenic acid, scutellarin, and scutellarein in MCAO rats had higher drug exposure than that in sham-operated rats, which provided a reference for the development of innovative drugs, optimal dosing regimens, and clinical rational drug use.

Sign in / Sign up

Export Citation Format

Share Document