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.

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.

Clopidogrel

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
Steady State ◽  
Oral Dose ◽  
Oral Administration ◽  
Randomized Clinical Trials ◽  
Peak Plasma ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Significant Inhibition ◽  
Inhibiting Effect ◽  
Dependent Inhibition

Clopidogrel, a thienopyridine derivative, is a novel platelet antagonist that is several times more potent than ticlopidine but associated with fewer adverse effects. After repeated 75-mg oral doses of clopidogrel, plasma concentrations of the parent compound, which has no platelet-inhibiting effect, are very low. Clopidogrel is extensively metabolized in the liver. The main circulating metabolite is a carboxylic acid derivative with a plasma elimination half-life of 7.7 ± 2.3 hours. Approximately 50% of an oral dose is excreted in the urine and the remaining 50% in feces over the following 5 days. Dose-dependent inhibition of platelet aggregation is observed 2 hours after a single oral dose of clopidogrel, with a more significant inhibition achieved with loading doses (≥300 mg) by approximately 6 hours. Repeated doses of 75 mg of clopidogrel per day inhibit adenosine diphosphate (ADP)-mediated aggregation, with steady state being reached between day 3 and day 7. At steady state, the average inhibition to ADP is between 40% and 60%. Based on ex vivo studies, clopidogrel is approximately 100-fold more potent than ticlopidine. There are no cumulative antiplatelet effects with prolonged oral administration. The combined administration of clopidogrel (300 mg loading dose) and aspirin yields a readily discernible platelet-inhibiting effect within 90 to 120 minutes. Clopidogrel selectively inhibits the binding of ADP to its platelet receptor (P2Y12) and the subsequent G-protein–linked mobilization of intracellular calcium and activation of the glycoprotein (GP)IIb/IIIa complex (Gachet et al., 1992). The specific receptor has been cloned and is abundantly present on the platelet surface (Hollopter et al., 2001). Clopidogrel has no direct effect on cyclooxygenase, phosphodiesterase, or adenosine uptake. Clopidogrel is rapidly absorbed following oral administration with peak plasma levels of the predominant circulating metabolite occurring approximately 60 minutes later. Administration with meals does not significantly modify the bioavailability of clopidogrel. The available information suggests that clopidogrel offers safety advantages over ticlopidine, particularly with regard to bone marrow suppression and other hematologic abnormalities. Although thrombotic thrombocytopenic purpura (TTP) has been reported with clopidogrel (Bennett et al., 2000), its occurrence (11 cases per 3 million patients treated) is rare, and has not been reported in randomized clinical trials performed to date.

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.

BIOLOGICAL HALF-LIFE OF CAFFEINE IN PIGS

1970 ◽  
Vol 50 (1) ◽  
pp. 49-54 ◽  
Author(s):  
H. M. CUNNINGHAM
Keyword(s):  
Oral Dose ◽  
Water Content ◽  
Single Oral Dose ◽  
Plasma Levels ◽  
Half Life ◽  
Intramuscular Injection ◽  
Peak Plasma ◽  
Growing Pigs ◽  
Sufficient Time ◽  
Biological Half Life

Five experiments were conducted with growing pigs to determine the biological half-life of caffeine after injection or various periods of ingestion. Peak plasma caffeine levels were reached within 5 hr after a single oral dose and 2 hr after intramuscular injection, and then declined with a biological half-life of about 12 hr. The caffeine content of tissues was approximately proportional to their water content and 6% of orally administered caffeine was excreted in the urine. Upon continuous ingestion of caffeine, peak plasma levels were reached within 2 days, indicating that accumulation was quite limited. When 1.5 g of caffeine per kg of feed was fed from weaning to market weight, the withdrawal of caffeine 2 days prior to slaughter was sufficient time to insure that caffeine levels in the liver, muscle, kidney and backfat were below 1 μg/g.

Human Pharmacology Studies in Volunteers with Indobufen (K 3920), Inhibitor of Platelet Aggregation

1979 ◽  
Author(s):  
L.M. Fuccella ◽  
G. Corvi ◽  
E. Pogliani ◽  
V. Tamassia ◽  
G. Tosolini ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Oral Administration ◽  
Healthy Volunteers ◽  
Kinetic Parameters ◽  
Plasma Levels ◽  
Half Life ◽  
Repeated Administration ◽  
Inhibitory Effect ◽  
Human Pharmacology ◽  
Unchanged Form

Given by the i.v. route to healthy volunteers, indobufen has an half-life of 7-9 h. After oral administration of tablets, the drug is completely absorbed. Excretion occurs through the kidney and the drug is present in the urine as glucoronide and in unchanged form. The maximum inhibitory effect on collagen-induced platelet aggregation was observed 1 to 4 h after i.v. and p.o. administration but activity at 8 h was more marked after p.o. administration in accordance with the higher plasma levels found at that time. During repeated administration at the dose of 100 mg b.i.d. for 7 days, no important changes in kinetic parameters and activity of indobufen was observed. Indobufen is rapidly absorbed also when given by the i.m. route, giving at 30 min peak levels comparable to those observed after oral administration. These data suggest that indobufen is active by the i.V., p.o. and i.m. routes, that its effect on platelets, unlike ASA, is reversible, and that its kinetics is linear.

Pharmacokinetic Evaluation of 3′-Azido-2′, 3′-Dideoxyuridine-5′-O-Valinate-Hydrochloride as a Prodrug of the Anti-HIV Nucleoside 3′-Azido-2′, 3′-Dideoxyuridine

2003 ◽  
Vol 14 (5) ◽  
pp. 263-270
Author(s):  
Linghui Kong ◽  
John S Cooperwood ◽  
Shu-Hui Christine Huang ◽  
Chung K Chu ◽  
F Douglas Boudinot
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Oral Bioavailability ◽  
Half Life ◽  
Dose Range ◽  
Parent Compound ◽  
Terminal Phase ◽  
Pharmacokinetic Parameters ◽  
Intravenous And Oral Administration ◽  
Anti Hiv

3′-Azido-2′, 3′-dideoxyuridine (AZDU, AzddU, CS-87) has been shown to have potent anti-HIV activity in vitro. However, the compound exhibits a relatively short half-life and incomplete oral bioavailability in humans. In an effort to improve the pharmacokinetic properties of AZDU, prodrug 3′-azido-2′,3′-dideoxyuridine-5′- O-valinate hydrochloride (AZDU-VAL) was synthesized by the esterification of 5′-OH function in AZDU. The objective of this study was to investigate the biotransformation and pharmacokinetics of AZDU-VAL along with its antiviral parent compound AZDU following intravenous and oral administration to rats. Adult male Sprague-Dawley rats were administered AZDU or AZDU-VAL by intravenous injection or oral gavage. Concentrations of AZDU-VAL and AZDU were determined by HPLC. Pharmacokinetic parameters were generated by area-moment analysis. The bioavailability of AZDU after oral administration was approximately 53%. The terminal phase half-life of the nucleoside analogue ranged between 0.6 h after intravenous administration and 1 h following oral administration. In vivo the prodrug was rapidly and efficiently biotransformed to yield AZDU following intravenous and oral administration. The apparent availability of AZDU was virtually complete following oral administration of prodrug AZDU-VAL averaging 101%. The bioavailability of AZDU following intravenous administration of AZDU-VAL averaged 106%. In summary, the disposition of AZDU was dose dependent over the dose range of 25–100 mg/kg. Renal clearance and steady state volume of distribution were lower at the higher dose level. Prodrug AZDU-VAL demonstrated improved oral bioavailability as evidenced by complete absorption and efficient bioconversion to AZDU. The results suggest that AZDU-VAL may be a promising prodrug for the delivery of AZDU.

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 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.

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