scholarly journals Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3069
Author(s):  
Yamen Alkhateeb ◽  
Qais Bashir Jarrar ◽  
Faridah Abas ◽  
Yaya Rukayadi ◽  
Chau Ling Tham ◽  
...  
Keyword(s):  
Area Under Curve ◽  
Intraperitoneal Administration ◽  
Bioactive Compound ◽  
Rat Plasma ◽  
Liquid Chromatography Mass Spectrometry ◽  
The Third ◽  
Glucuronide Conjugation ◽  
Accuracy And Precision ◽  
Elimination Half ◽  
Time Required

2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5–80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life (t1/2) and area under curve (AUC0–24) values for intraperitoneal administration were 54.6 ng/mL, 1.5 h, 6.7 h, and 193.9 ng/mL·h, respectively. For the oral administration of unformulated and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0–24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.

Development of an Acute Model for the Study of Chloromethanediphosphonate Nephrotoxicity

1989 ◽  
Vol 17 (1_part_1) ◽  
pp. 27-32 ◽  
Author(s):  
Carl L. Alden ◽  
Ronald D. Parker ◽  
David F. Eastman
Keyword(s):  
Renal Toxicity ◽  
Intraperitoneal Administration ◽  
Tubular Epithelium ◽  
The Third ◽  
Pars Recta ◽  
Proximal Tubular ◽  
Histopathologic Changes ◽  
Time Required ◽  
Proximal Tubular Epithelium ◽  
Phosphorus Levels

Chloromethanediphosphonate (Cl2MDP), a cation chelator, is used as a therapeutic for hypercalcemia of malignancy. Cl2MDP exhibits nephrotoxic potential. Thus, a useful model has been developed to study the mechanism of injury. Intraperitoneal administration of highly exaggerated dosages, specifically 200 mg/kg b.i.d., resulted in a consistent mild to moderate extent of kidney damage after the third day of treatment in rats. Proteinuria and lowered serum phosphorus levels occur prior to onset of histopathologic changes. Injury was characterized as necrosis of proximal tubular epithelium with predilection for pars recta. Unlike many renal toxicity models, the necrosis occurs as cell lysis only after 24 to 48 hours of treatment. However, this model significantly reduces the time required to induce renal toxicity observed in routine toxicity studies from months of treatment to less than 1 week and will, thus, serve as a baseline for subsequent pathogenetic studies.

Studies on the life-history of Bunostomum phlebotomum (Railliet, 1900), a hookworm parasite of cattle

Parasitology ◽  
1946 ◽  
Vol 37 (3-4) ◽  
pp. 192-201 ◽  
Author(s):  
J. F. A. Sprent
Keyword(s):  
Infective Larva ◽  
Stage Larva ◽  
Fourth Stage ◽  
Larval Stages ◽  
The Third ◽  
Third Stage ◽  
History Of ◽  
Time Required ◽  
Cutaneous Blood ◽  
Fourth Stage Larva

A description is given of the processes of copulation, formation of the egg and spermatozoon, cleavage, embryogeny and hatching in B. phlebotomum. These processes were found to be essentially similar to those in other strongyle nematodes.The anatomy of the first three larval stages is described and the observations of Conradi & Barnette (1908) and Schwartz (1924) were largely confirmed.Penetration of the skin of calves by the infective larva was observed histologically. The larvae were found to have reached the dermis within 30 min. and to have penetrated the cutaneous blood vessels within 60 min. of application to the skin. The larvae were found in the lung where the third ecdysis was in progress 10 days after penetration of the skin. A description is given of the growth of the third-stage larva in the lung, the changes which take place during the third ecdysis, and the anatomy of the fourth-stage larva.The fourth-stage larvae exsheath in the lungs and travel to the intestine. After a period of growth in which sexual differentiation takes place, the fourth ecdysis occurs and the adult parasite emerges. The time required for the attainment of maturity was found to be somewhere between 30 and 56 days after penetration of the skin.This paper was written at the Ministry of Agriculture and Fisheries Veterinary Laboratories, Wey-bridge, and the writer would like to express his gratitude to the Director, Prof. T. Dalling, also to Dr W. R. Wooldridge, chairman of the Council of the Veterinary Educational Trust for their help and encouragement. The writer's thanks are also due to Dr H. A. Baylis, Prof. R. T. Leiper and Dr E. L. Taylor for their advice and help on technical points, and to Mr R. A. O. Shonekan, African laboratory assistant, for his able co-operation.

scholarly journals Milk and Blood Pharmacokinetics of Tylosin and Tilmicosin following Parenteral Administrations to Cows

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Tulay Avci ◽  
Muammer Elmas
Keyword(s):  
Peak Concentration ◽  
Subcutaneous Administration ◽  
Parenteral Administration ◽  
Intramuscular Administration ◽  
Withdrawal Period ◽  
Holstein Breed ◽  
Elimination Half ◽  
Time Required

The aim of this study is to determine the pharmacokinetics of tylosin and tilmicosin in serum and milk in healthy Holstein breed cows (n=12) and reevaluate the amount of residue in milk. Following the intramuscular administration of tylosin, the maximum concentrations (Cmax) in serum and milk were found to be1.30±0.24and4.55±0.23 µg/mL, the time required to reach the peak concentration (tmax) was found to be 2nd and 4th h, and elimination half-lives (t1/2β) were found to be20.46±2.08and26.36±5.55 h, respectively. Following the subcutaneous administration of tilmicosin, theCmaxin serum and milk were found to be0.86±0.20and20.16±1.13 µg/mL, thetmaxwas found to be 1st and 8th h, and thet1/2βwere found to be29.94±6.65and43.02±5.18 h, respectively.AUCmilk/AUCserumandCmax-milk/Cmax-serumrates, which are indicators for determining the rate of drugs that pass into milk, were, respectively, calculated as5.01±0.72and3.61±0.69for tylosin and23.91±6.38and20.16±1.13for tilmicosin. In conclusion, it may be stated that milk concentration of tylosin after parenteral administration is higher than expected like tilmicosin and needs more withdrawal period for milk than reported.

scholarly journals Pharmacodynamics of a Long-Acting Echinocandin, CD101, in a Neutropenic Invasive-Candidiasis Murine Model Using an Extended-Interval Dosing Design

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Alexander J. Lepak ◽  
Miao Zhao ◽  
Brian VanScoy ◽  
Paul G. Ambrose ◽  
David R. Andes
Keyword(s):  
Invasive Candidiasis ◽  
Half Life ◽  
Intraperitoneal Administration ◽  
Time Curve ◽  
Content Type ◽  
Elimination Half ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Long Acting

ABSTRACT Echinocandins are important in the prevention and treatment of invasive candidiasis but limited by current dosing regimens that include daily intravenous administration. The novel echinocandin CD101 has a prolonged half-life of approximately 130 h in humans, making it possible to design once-weekly dosing strategies. The present study examined the pharmacodynamic activity of CD101 using the neutropenic invasive candidiasis mouse model against select Candida albicans (n = 4), C. glabrata (n = 3), and C. parapsilosis (n = 3) strains. The CD101 MIC ranged from 0.03 to 1 mg/liter. Plasma pharmacokinetic measurements were performed using uninfected mice after intraperitoneal administration of 1, 4, 16, and 64 mg/kg. The elimination half-life was prolonged at 28 to 41 h. Neutropenic mice were infected with each strain by lateral tail vein injection, treated with a single dose of CD101, and monitored for 7 days, at which time the organism burden was enumerated from the kidneys. Dose-dependent activity was observed for each organism. The pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC index) correlated well with efficacy (R 2, 0.74 to 0.93). The median stasis 24-h free-drug AUC/MIC targets were as follows: for C. albicans, 2.92; for C. glabrata, 0.07; and for C. parapsilosis, 2.61. The PK/PD targets for 1-log10 kill endpoint were 2- to 4-fold higher. Interestingly, the aforementioned PK/PD targets of CD101 were numerically lower for all three species than those of other echinocandins. In summary, CD101 is a promising, novel echinocandin with advantageous pharmacokinetic properties and potent in vivo pharmacodynamic activity.

scholarly journals Toxicity and Pharmacokinetic Studies of Lidocaine and Its Active Metabolite, Monoethylglycinexylidide, in Goat Kids

Animals ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 142
Author(s):  
Dinakaran Venkatachalam ◽  
Paul Chambers ◽  
Kavitha Kongara ◽  
Preet Singh
Keyword(s):  
Total Dose ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Lidocaine Hydrochloride ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Liquid Chromatography Mass Spectrometry ◽  
Elimination Half ◽  
The Mean ◽  
Safe Dose

This study determined the convulsant plasma concentrations and pharmacokinetic parameters following cornual nerve block and compared the results to recommend a safe dose of lidocaine hydrochloride for goat kids. The plasma concentrations of lidocaine and monoethylglycinexylidide (MGX) were quantified using liquid chromatography-mass spectrometry. A total dose of 7 mg/kg body weight (BW) was tolerated and should therefore be safe for local and regional anesthesia in goat kids. The mean plasma concentration and mean total dose that produced convulsions in goat kids were 13.59 ± 2.34 µg/mL and 12.31 ± 1.42 mg/kg BW (mean ± S.D.), respectively. The absorption of lidocaine following subcutaneous administration was rapid with Cmax and Tmax of 2.12 ± 0.81 µg/mL and 0.33 ± 0.11 h, respectively. The elimination half-lives (t½λz) of lidocaine hydrochloride and MGX were 1.71 ± 0.51 h and 3.19 ± 1.21 h, respectively. Injection of 1% lidocaine hydrochloride (0.5 mL/site) was safe and effective in blocking the nerves supplying horn buds in goat kids.

scholarly journals HILL CIPHER ON SHAMIR’S THREE PASS PROTOCOL

2017 ◽  
Author(s):  
hasdiana
Keyword(s):  
Matrix Element ◽  
Execution Time ◽  
Invertible Matrix ◽  
Multidisciplinary Research ◽  
The Third ◽  
Xor Operation ◽  
Hill Cipher ◽  
The Matrix ◽  
Level Of Difficulty ◽  
Time Required

This preprint has been presented in the 3rd International Conference on Multidisciplinary Research, Medan, october 16 – 18, 2014---In this study the authors use the scheme of Shamir's Three Pass Protocol for Hill Cipher operation. Scheme of Shamir's Three Pass Protocol is an attractive scheme that allows senders and receivers to communicate without the key exchange. Hill Cipher is chosen because of the key-shaped matrix, which is expected to complicate the various techniques of cryptanalyst. The results of this study indicate that the weakness of the scheme of Shamir's Three Pass Protocol for XOR operation is not fully valid if it is used for Hill Cipher operations. Cryptanalyst can utilize only the third ciphertext that invertible. Matrix transpose techniques in the ciphertext aims to difficulties in solving this algorithm. The original ciphertext generated in each process is different from the transmitted ciphertext. The level of difficulty increases due to the use of larger key matrix. The amount of time required for the execution of the program depends on the length of the plaintext and the value of the matrix element. Plaintext has the same length produce different execution time depending on the value of the key elements of the matrix used.

scholarly journals Spectrophotometric Determination of Olmutinib in Bulk by Area under Curve and First Order Derivative Methods and its Validation as per ICH guidelines

2019 ◽  
Vol 9 (4-A) ◽  
pp. 349-354
Author(s):  
BALU KHANDARE ◽  
Atish C. Musle ◽  
Sanket S. Arole ◽  
Pravin V. Popalghat
Keyword(s):  
Area Under Curve ◽  
Limit Of Detection ◽  
Order Derivative ◽  
Spectrometric Method ◽  
First Order ◽  
Accuracy And Precision ◽  
Ich Guidelines ◽  
Validation Parameters ◽  
Limit Of Quantitation

Abstract: A simple, precise and economical UV-spectrophotometric method has been developed for the estimation of Olmutinib from bulk. Two methods were developed First method (A) applied was area under curve (AUC) in which the area was integrated in wavelength from 262-272nm. Second method (B) was first order derivative spectrometric method. In this method absorbance at λmin=256.57nm, λmax=282.83nm and zero cross=267.68nm was measured. Calibration curves were plotted for the method by using instrumental response at selected wavelength and concentration of analyte in the solution. In both the methods, linearity was observed in the concentration range of 2-12µg/ml at the λmax=267.68nm. Accuracy and precision studies were carried out and results were satisfactorily obtained. The drug at each of the 80 %, 100 % and 120 % levels showed good recoveries that is in the range of 98.00 to 99.00% for both methods, hence it could be said that the method was accurate. Limit of detection (LOD) and limit of quantitation (LOQ) were determined for the method. The method was validated as per International Conference on Harmonization. All validation parameters were within the acceptable limit. The developed method was successfully applied to estimate the amount of Olmutinib in pharmaceutical formulation.

scholarly journals Pharmacokinetics of isocorynoxeine in rat plasma after intraperitoneal administration by UPLC–MS/MS

2020 ◽  
Vol 32 (4) ◽  
pp. 260-263
Author(s):  
Haichao Zhan ◽  
Zhen Wei ◽  
Ke Ren ◽  
Shuhua Tong ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Intraperitoneal Administration ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Isocorynoxeine is one of the main alkaloids in Chinese medicinal herbs, and has pharmacological activities such as antihypertensive, sedative, anticonvulsant, and neuronal protection. It is an effective component of Uncaria for the treatment of hypertension. In this study, we used a fast and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to detect isocorynoxeine in rat plasma and investigated its pharmacokinetics in rats. Six rats were given isocorynoxeine (15 mg/kg) by intraperitoneal (i.p.) administration. Blood (100 μL) was withdrawn from the caudal vein at 5 and 30 min and 1, 2, 4, 6, 8, 12, and 24 h after administration. Chromatographic separation was achieved using a UPLC BEH C18 column using a mobile phase of acetonitrile–0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with positive ionization was applied. Intra-day and inter-day precisions (relative standard deviation, %RSD) of isocorynoxeine in rat plasma were lower than 12%. The method was successfully applied in the pharmacokinetics of isocorynoxeine in rats after intraperitoneal administration. The t1/2 of isocorynoxeine is 4.9 ± 2.1 h, which indicates quick elimination.

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