Pharmacokinetics of the prodrug thiamphenicol glycinate and its active parent compound thiamphenicol in beagle dogs following intravenous administration

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.

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The Effects of Intravenous Administration of 10% Travamulsion Fat Emulsion to Beagle Dogs for 91 Consecutive Days

Journal of Parenteral and Enteral Nutrition ◽

10.1177/0148607183007003257 ◽

1983 ◽

Vol 7 (3) ◽

pp. 257-265 ◽

Cited By ~ 3

Author(s):

Rodger S. Izzo ◽

Nancy Leissing ◽

Eugene Woods ◽

William Remis ◽

Martha Napoli ◽

...

Keyword(s):

Intravenous Administration ◽

Beagle Dogs ◽

Fat Emulsion

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Absorption and Excretion of 17, 21-Dihydroxy-20-Ketosteroids in Dogs

Clinical Chemistry ◽

10.1093/clinchem/2.3.170 ◽

1956 ◽

Vol 2 (3) ◽

pp. 170-174 ◽

Cited By ~ 15

Author(s):

Robert H Silber ◽

Evan R Morgan

Keyword(s):

Double Bond ◽

Urinary Excretion ◽

Intravenous Administration ◽

Half Life ◽

Parent Compound ◽

Plasma Concentrations ◽

Plasma Half Life

Abstract The plasma concentrations of free 17,21-dihydroxy-20-ketosteroids and urinary excretion of both free and glucuronide forms have been determined after oral, intramuscular, and intravenous administration of cortisone, hydrocortisone, their δ1 forms, and 9α-fluorohydrocortisone to dogs. Excretion of the glucuronide forms of those steroids with a double bond at the 1-2 position or with a fluorine at position 9 was depressed, and the plasma half-life of each of these steroids was longer than that of the parent compound.

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Role of mitochondrial and sarcolemmal KATPchannels in ischemic preconditioning of the canine heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.1.h256 ◽

2001 ◽

Vol 280 (1) ◽

pp. H256-H263 ◽

Cited By ~ 48

Author(s):

Shoji Sanada ◽

Masafumi Kitakaze ◽

Hiroshi Asanuma ◽

Kengo Harada ◽

Hisakazu Ogita ◽

...

Keyword(s):

Infarct Size ◽

Intravenous Administration ◽

Ischemic Preconditioning ◽

Channel Blocker ◽

Control Group ◽

Canine Heart ◽

Beagle Dogs ◽

Left Anterior Descending Artery ◽

Channel Opener

We tested whether mitochondrial or sarcolemmal ATP-sensitive K+(KATP) channels play a key role in ischemic preconditioning (IP) in canine hearts. In open-chest beagle dogs, the left anterior descending artery was occluded four times for 5 min each with 5-min intervals of reperfusion (IP), occluded for 90 min, and reperfused for 6 h. IP as well as cromakalim and nicorandil (nonspecific KATP channel openers) markedly limited infarct size (6.3 ± 1.2, 8.9 ± 1.9, and 7.2 ± 1.6%, respectively) compared with the control group (40.9 ± 4.1%). A selective mitochondrial KATP channel blocker, 5-hydroxydecanoate, partially blunted the limitation of infarct size in the animals subjected to IP and those treated with cromakalim and nicorandil (21.6 ± 3.8, 25.1 ± 4.6, and 19.8 ± 5.2%, respectively). A nonspecific KATP channel blocker, glibenclamide, completely abolished the effect of IP (38.5 ± 6.2%). Intracoronary or intravenous administration of a mitochondria-selective KATP channel opener, diazoxide, at >100 μmol/l could only partially decrease infarct size (19.5 ± 4.3 and 20.1 ± 4.4%, respectively). In conclusion, mitochondrial and sarcolemmal KATP channels independently play an important role in the limitation of infarct size by IP in the canine heart.

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