Pharmacokinetics and Tissue Distribution of Aegeline after Oral Administration in Mice

Planta Medica ◽  
2019 ◽  
Vol 85 (06) ◽  
pp. 491-495
Author(s):  
Vamshi Manda ◽  
Mona Haron ◽  
Tahir Mir ◽  
Bharathi Avula ◽  
Mohammad Ashfaq ◽  
...  
Keyword(s):  
Oral Administration ◽  
Tissue Distribution ◽  
Half Life ◽  
Therapeutic Potential ◽  
Peak Plasma ◽  
Biologically Active ◽  
Active Constituent ◽  
Peak Plasma Level ◽  
Tissue Samples ◽  
Obesity And Diabetes

AbstractAegeline is claimed to be a biologically active constituent of Aegle marmelos. Preclinical studies have reported possible therapeutic potential for aegeline against obesity and diabetes. In recent years, aegeline has been added to several weight loss products. However, the consumption of aegeline-containing supplements such as OxyELITE Pro and VERSA-1 has been linked to multiple cases of acute and chronic liver failure. This study was carried out to evaluate the pharmacokinetics and tissue distribution of aegeline in ND4 mice. Two doses of aegeline, a human equivalent dose (1×) 30 mg/kg and a 10× dose (300 mg/kg), were orally administered to the mice, and blood and tissue samples were collected over 8 h. The quantitative analysis of plasma and tissue homogenates (liver, kidney, and brain) was done by UHPLC-QTOF to determine aegeline concentrations. The peak plasma level of aegeline was achieved at a Tmax of 0.5 h, indicating its rapid absorption from the gastrointestinal tract. Aegeline was not detected in the plasma at 8 h after oral administration, with a half-life of 1.4 ± 0.01 and 1.3 ± 0.07 h for the 30 and 300 mg/kg doses, respectively. The half-life of aegeline in the liver was 1.2 h and 1.7 h for 30 and 300 mg/kg doses, respectively, with a Tmax of 1.9 h, which indicates relatively fast elimination of aegeline from the liver.

Absorption, Tissue Distribution and Elimination of 4-[3H]-Epigallocatechin Gallate in Beagle Dogs

2003 ◽  
Vol 22 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Robert R. Swezey ◽  
Daphne E. Aldridge ◽  
Susanna E. Le Valley ◽  
James A. Crowell ◽  
Yukihiko Hara ◽  
...  
Keyword(s):  
Oral Administration ◽  
Tissue Distribution ◽  
Plasma Levels ◽  
Half Life ◽  
Peak Plasma ◽  
Parent Compound ◽  
Epigallocatechin Gallate ◽  
Total Radioactivity ◽  
Repeat Dose ◽  
Beagle Dogs

Polyphenols found in tea are potent antioxidants and have inhibitory activity against tumorigenicity. The purpose of the described study was to assess the absorption, tissue distribution, and elimination of epigallocatechin gallate (EGCG), the principal catechin found in green tea, in a nonrodent species. 4-[3H]-EGCG was administered to beagle dogs by intravenous (IV) and oral routes. Following IV administration of 25 mg/kg, radioactivity in the bloodstream resided predominantly in the plasma. Distribution occurred during the first hour, and the plasma levels of total radioactivity declined with a mean half-life of approximately 7 hours. The apparent volume of distribution (0.65 l/kg) indicated wide distribution, and the total body clearance (1.01 ml/min-kg) was low. A subsequent single oral dose (250 mg/kg) was rapidly absorbed, with peak plasma levels at about 1 hour after administration, followed by elimination with a mean half-life of 8.61 hours. The mean area under the curve (AUC) for total radioactivity was approximately 20% of the value following IV administration (corrected for dose administered). Excretion of radioactivity in the feces predominated over urinary excretion following both IV and oral administration of [3H]-EGCG. Tissue distribution was determined 1 hour after an IV dose (25 mg/kg) administered after 27 days of oral treatment with EGCG (250 mg/kg/day) to mimic chronic consumption of tea. Radioactivity was distributed to a variety of epithelial tissues; the highest concentrations were observed in the liver and gastrointestinal tract tissues. Repeat dose oral administration of EGCG resulted in significantly lower blood radioactivity compared to the concentration following a single dose. These results are generally in accord with previous studies in rodents and indicate that, after oral administration, EGCG (as parent compound and metabolites) is widely distributed to tissues where it can exert a chemopreventive effect.

Tissue Distribution and Renal Excretion of Ormetoprim after Intravascular and Oral Administration in the Channel Catfish (Ictalurus punctatus)

1990 ◽  
Vol 47 (4) ◽  
pp. 766-771 ◽  
Author(s):  
S. M. Plakas ◽  
R. W. Dickey ◽  
M. G. Barron ◽  
A. M. Guarino
Keyword(s):  
Oral Administration ◽  
Ictalurus Punctatus ◽  
Channel Catfish ◽  
Renal Excretion ◽  
Peak Plasma ◽  
Parent Compound ◽  
Head Kidney ◽  
Peak Plasma Level ◽  
Bacterial Diseases ◽  
A Minor

Ormetoprim is used to potentiate sulfadimethoxine in treating certain bacterial diseases of aquatic species. The tissue disposition and renal excretion of ormetoprim and metabolites were examined after intravascular and oral administration (4 mg∙kg−1) in channel catfish (Ictalurus punctatus). Peak plasma level (0.66 μg∙mL−1) of 14C-ormetoprim occurred at 6 h after oral dosing. The oral bioavailability was estimated at 52%. Ormetoprim and metabolites were widely distributed in the tissues. The tissue concentrations were highest in the liver, trunk kidney, head kidney, and spleen. Clearance of the radiolabel from tissues was rapid. The muscle contained 49.3% of the intravascularly administered dose at 2 h; however, at 72 h, less than 1% of the dose remained in this tissue. 14C-Ormetoprim was more persistent in the skin than in the muscle. Ormetoprim was extensively metabolized in catfish. After intravascular administration, 21.1% of the dose of 14C-ormetoprim was eliminated in the urine in 48 h, predominantly as polar metabolites; less than 4% of the dose was eliminated as the parent compound. Biliary excretion was a minor route of elimination (5–6% of the dose). The data suggest branchial excretion of ormetoprim and/or metabolites.

scholarly journals Antioxidant and Hepatoprotective Effects of Silibinin in a Rat Model of Nonalcoholic Steatohepatitis

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Yara Haddad ◽  
Diane Vallerand ◽  
Antoine Brault ◽  
Pierre S. Haddad
Keyword(s):  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Therapeutic Potential ◽  
Liver Steatosis ◽  
Liver Weight ◽  
Liquid Diet ◽  
Biologically Active ◽  
Control Group ◽  
The Metabolic Syndrome ◽  
Obesity And Diabetes

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease related to the metabolic syndrome, obesity and diabetes. The rising prevalence of NASH and the lack of efficient treatments have led to the exploration of different therapeutic approaches. Milk thistle (Silibum marianum) is a medicinal plant used for its hepatoprotective properties in chronic liver disease since the 4th century BC. We explored the therapeutic effect of silibinin, the plant's most biologically active extract, in an experimental rat NASH model. A control group was fed a standard liquid diet for 12 weeks. The other groups were fed a high-fat liquid diet for 12 weeks without (NASH) or with simultaneous daily supplement with silibinin–phosphatidylcholine complex (Silibinin 200 mg kg−1) for the last 5 weeks. NASH rats developed all key hallmarks of the pathology. Treatment with silibinin improved liver steatosis and inflammation and decreased NASH-induced lipid peroxidation, plasma insulin and TNF-α. Silibinin also decreasedO2∙-release and returned the relative liver weight as well as GSH back to normal. Our results suggest that milk thistle's extract, silibinin, possesses antioxidant, hypoinsulinemic and hepatoprotective properties that act against NASH-induced liver damage. This medicinal herb thus shows promising therapeutic potential for the treatment of NASH.

scholarly journals Safety and Pharmacokinetics of Bevirimat (PA-457), a Novel Inhibitor of Human Immunodeficiency Virus Maturation, in Healthy Volunteers

2007 ◽  
Vol 51 (9) ◽  
pp. 3063-3066 ◽  
Author(s):  
David E. Martin ◽  
Robert Blum ◽  
John Wilton ◽  
Judy Doto ◽  
Hal Galbraith ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Oral Administration ◽  
Half Life ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Double Blind Study ◽  
Immunodeficiency Virus ◽  
Oral Doses

ABSTRACT Bevirimat (BVM; formerly known as PA-457) is a novel inhibitor of human immunodeficiency virus (HIV) maturation that is being developed for the treatment of HIV infection. The pharmacokinetics of this agent in healthy male volunteers were studied in a randomized, double-blind study in which the participants received single oral doses of placebo (n = 8) or escalating doses of BVM at 25, 50, 100, or 250 mg (n = 6 per dose); escalation was performed only after the pharmacokinetics and safety of the preceding dose had been evaluated. Plasma was collected over 480 h after dosing and urine was collected over 48 h after dosing for determination of the values of pharmacokinetic parameters. BVM was well absorbed after oral administration, with peak plasma concentrations being achieved 1 to 3 h after dosing. The half-life was 60 to 80 h. The exposure assessed by determination of the peak concentration and the area under the concentration-time curve was dose proportional. Single oral doses of BVM were well tolerated: there were no dose-limiting toxicities, and no serious adverse events were reported. These findings suggest that that BVM offers a favorable pharmacokinetic profile, with predictable pharmacokinetics following the oral administration of single doses. The long half-life of BVM may facilitate once-daily dosing.

scholarly journals Pharmacokinetic Study and Tissue Distribution of Lorlatinib in Mouse Serum and Tissue Samples by Liquid Chromatography-Mass Spectrometry

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Wei Chen ◽  
Yafei Shi ◽  
Shuya Qi ◽  
Haiyan Zhou ◽  
Chunyu Li ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Oral Administration ◽  
Tissue Distribution ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Mouse Serum ◽  
Simple Liquid ◽  
Tissue Samples

In the present study, we developed and validated a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of lorlatinib in mouse serum and tissue samples, and such a method was successfully applied to investigate the pharmacokinetic study and tissue distribution of lorlatinib after oral administration. Samples were processed with methanol to precipitate protein and extract drugs, and Afatinib-d6 was used as the internal standard (IS). For LC-MS/MS analysis, compounds were separated on a C18 column by gradient elution (0.1% of formic acid and methanol) at 0.5 mL/min in the positive-ion mode with m/z 407.28 [M + H]+ for lorlatinib and m/z 492.10 [M + H]+ for IS. Good linearity was observed within the calibration ranges. Selectivity, accuracy (−6.42% to 8.84%), precision (1.69% to 10.98%), recoveries (91.4% to 115.0%), and matrix effect (84.2% to 110.6%) were all within the acceptable ranges. After oral administration, serum concentration of lorlatinib quickly achieved the maximal concentration (2,705.683 ± 539.779 μg/L) at 0.625 ± 0.231 h. The highest concentration was detected in the liver (3,153.93 ng/100 mg), followed by the stomach (2,159.92 ng/100 mg) and the kidney (548.83 ng/100 mg). In conclusion, a simple and rapid detection method was established and validated for determination of lorlatinib in blood and tissue samples of mouse. The pharmacokinetic study and tissue distribution of lorlatinib were successfully investigated using this method.

scholarly journals A Pharmacokinetic Study of Antimalarial 3,5-Diaryl-2-aminopyridine Derivatives

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Ntokozo Dambuza ◽  
Peter Smith ◽  
Alicia Evans ◽  
Dale Taylor ◽  
Kelly Chibale ◽  
...  
Keyword(s):  
Half Life ◽  
Peak Plasma ◽  
World Health ◽  
African Region ◽  
Peak Plasma Level ◽  
Drug Candidates ◽  
The World ◽  
The Mean ◽  
Health Organization ◽  
Derivatives Of

Malaria caused by Plasmodium falciparum is responsible for approximately 80% of the incidence and 90% of deaths which occur in the World Health Organization (WHO) African region, with children and pregnant women having the highest incidence. P. falciparum has developed resistance, and therefore new effective candidate antimalarial drugs need to be developed. Previous studies identified 3,5-diaryl-2-aminopyridines as potential antimalarial drug candidates; therefore, derivatives of these compounds were synthesized in order to improve their desired properties and pharmacokinetic (PK) properties of the derivatives were investigated in a mouse model which was dosed orally and intravenously. Collected blood samples were analyzed using liquid chromatography coupled to mass spectrometer (LC-MS/MS). The mean peak plasma level of 1.9 μM was obtained at 1 hour for compound 1 and 3.3 μM at 0.5 hours for compound 2. A decline in concentration was observed with a half-life of 2.53 and 0.87 hours for compound 1 in mice dosed orally and intravenously, respectively. For compound 2 a half-life of 2.96 and 0.68 hours was recorded. The bioavailability was 69% and 59.7% for compound 1 and compound 2, respectively.

Oral Administration of Carbon-14 Labeled Cyanocobalamin (14C-Cbl) Reveals Variable Degradation of Vitamin B12 in the Gastrointestinal Tract That Impacts Vitamin B12 Absorption and Status.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3018-3018
Author(s):  
Ralph Green ◽  
Joshua W Miller ◽  
Kyung-Seon Lee ◽  
Syrukh Sutter ◽  
Lindsay H Allen ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Plasma Level ◽  
Oral Administration ◽  
Urinary Excretion ◽  
Vitamin B12 ◽  
Research Funding ◽  
Peak Plasma ◽  
Science Research ◽  
Fecal Excretion ◽  
Peak Plasma Level

Abstract Abstract 3018 Poster Board II-994 Recent evidence from our laboratory and others suggests that a variable portion of ingested cobalamin (Cbl), either crystalline or from food, is degraded in the gastrointestinal tract. We have developed a biosynthetic method to incorporate 14C into the lower axial ligand of cobalamin that has made it possible to study the fate of this vitamin during its passage through the gastrointestinal tract and to assess the presence of Cbl or its breakdown products in biological samples. Following oral administration of an aqueous physiological tracer dose of 14C-Cbl (1.3 μg, 50 nCi), blood, urine, and feces are analyzed for 14C by accelerator mass spectrometry. In 9 subjects, the plasma response was consistent with the expected behavior of peroral Cbl: 14C-Cbl first appeared in the plasma 3h post-dose reaching a peak level within 6-8h. Confirmation that this dose appears bound to the physiological transport protein transcobalamin (TC) was obtained in a subset of subjects by an immunoaffinity method using anti-human TC antibody-coated magnetic beads which selectively bound 95-98% of plasma 14C. Urinary excretion of 14C was maximal in the first 24h, with 14C first appearing in urine as early as 1.5h after dosing. Fecal excretion occurred variably over several days. The amount of 14C found in the urine (10-50% of the dose) was 100-fold greater than in previous reports using 57Co-labeled cyanocobalamin (0.1-0.5%), and fecal excretion was lower than expected (10-20% vs 30-70%). Urinary excretion of 14C was inversely correlated with the peak plasma level of 14C attained (r2=0.610; p<0.001). The bulk of urinary 14C was not associated with intact Cbl and first appeared in the urine before peak 14C levels were attained in the plasma. The peak plasma level of 14C attained also showed a strong positive correlation with plasma holotranscobalamin concentration measured before administration of the 14C-Cbl (r2=0.571; p<0.001). No such correlation was found with total plasma Cbl. In additional experiments on normal volunteers using eggs endogenously labeled with 14C Cbl following intramuscular injection of hens with 14C Cbl, comparably high urinary excretion of 14C was also observed. We conclude that a variable fraction of ingested Cbl is degraded in the gastrointestinal tract of normal individuals. This may be an important determinant of the amount of Cbl absorbed from food or supplement sources. Additionally, our findings suggest that the concentration of holoTC in the plasma reflects absorptive capacity and may therefore be a good surrogate for Cbl absorptive status. Our findings also have implications regarding the bioavailability of Cbl and may inform pending considerations to fortify food supplies with Cbl in order to mitigate the incidence of Cbl deficiency, particularly among the elderly. Intestinal degradation, either microbial or through the action of digestive enzymes, may also be a source of Cbl analogues that have previously been detected in the plasma and tissues. Cbl analogues may interfere with the physiological function of cobalamin, resulting in some of the manifestations of cobalamin deficiency. Disclosures: Green: Vitalea Science: Research Funding. Miller:Vitalea Science: Research Funding. Lee:Vitalea Science: Research Funding. Sutter:Vitalea Science: Research Funding. Allen:Vitalea Science: Research Funding. Dueker:Vitalea Science: Employment.

Azithromycin: An Assessment of Its Pharmacokinetics and Therapeutic Potential in CAPD

2001 ◽  
Vol 21 (4) ◽  
pp. 372-377 ◽  
Author(s):  
James R. Kent ◽  
Michael K. Almond ◽  
Soraya Dhillon
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Therapeutic Potential ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Future Research ◽  
Renal Unit ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean

Background Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity. Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin. This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Objective This study aimed to define the potential role of azithromycin in treating CAPD peritonitis. Design The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin. Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography. Setting The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom. Patients Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day). Results Peak plasma concentrations occurred at 2 -3 hours with 0.35 - 1.35 mg/mL (mean 0.75). The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8 hours, the mean dialysate concentration was 0.07 mg/mL; PD clearance was 0.06 L/hr. Conclusion Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present. However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported. Future research should address this possibility.

scholarly journals Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 124 ◽  
Author(s):  
Zhi-Yuan Zhang ◽  
Hua Zhang ◽  
Dan Liu ◽  
Ying-Yuan Lu ◽  
Xin Wang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Tissue Distribution ◽  
High Performance ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Pharmacokinetic Profile ◽  
Rat Plasma ◽  
Drug Candidate ◽  
Liquid Chromatography Tandem Mass

Methyl 3-amino-6-methoxythieno [2,3-b] quinoline-2-carboxylate (PU-48) is a novel diuretic urea transporter inhibitor. The aim of this study is to investigate the profile of plasma pharmacokinetics, tissue distribution, and excretion by oral dosing of PU-48 in rats. Concentrations of PU-48 within biological samples are determined using a validated high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. After oral administration of PU-48 (3, 6, and 12 mg/kg, respectively) in self-nanomicroemulsifying drug delivery system (SNEDDS) formulation, the peak plasma concentrations (Cmax), and the area under the curve (AUC0–∞) were increased by the dose-dependent and linear manner, but the marked different of plasma half-life (t1/2) were not observed. This suggests that the pharmacokinetic profile of PU-48 prototype was first-order elimination kinetic characteristics within the oral three doses range in rat plasma. Moreover, the prototype of PU-48 was rapidly and extensively distributed into thirteen tissues, especially higher concentrations were detected in stomach, intestine, liver, kidney, and bladder. The total accumulative excretion of PU-48 in the urine, feces, and bile was less than 2%. This research is the first report on disposition via oral administration of PU-48 in rats, and it provides important information for further development of PU-48 as a diuretic drug candidate.

scholarly journals LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3342 ◽  
Author(s):  
Yang Li ◽  
Chenxi Guang ◽  
Na Zhao ◽  
Xinchi Feng ◽  
Feng Qiu
Keyword(s):  
Oral Administration ◽  
Formic Acid ◽  
Tissue Distribution ◽  
Electrospray Ionization ◽  
Liver Tissue ◽  
Tandem Mass ◽  
Tissue Samples ◽  
Distribution Study ◽  
Tissue Distribution Study

Linarin, a flavone glycoside, is considered to be a promising natural product due to its diverse pharmacological activities. Recently, it has been brought into focus for its potential to treat liver failure. In this study, a rapid and sensitive liquid chromatography electrospray-ionization tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of linarin and its three metabolites (acacetin, apigenin, and p-hydroxy benzaldehyde) in plasma and liver tissue samples of normal rats and rats with d-galactosamine (d-GalN)-induced liver injury. After liquid–liquid extraction (LLE) with ethyl acetate, chromatographic separation of the four analytes was achieved using an ACQUITY UPLC BEH-C18 (1.7 μm, 2.1 × 50 mm) with a mobile phase of 0.01% formic acid in methanol and 0.01% formic acid at a flow rate of 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer via an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in the negative ionization mode. The method had a good linearity over the concentration range of 1.00–200 ng/mL for linarin and its metabolites. The validated method was successfully applied to the pharmacokinetic and liver tissue distribution study of linarin and its metabolites after a single oral administration of linarin (90 mg/kg) to rats.

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