Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract

1986 ◽  
Vol 251 (3) ◽  
pp. G332-G340 ◽  
Author(s):  
J. A. Fix ◽  
K. Engle ◽  
P. A. Porter ◽  
P. S. Leppert ◽  
S. J. Selk ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Drug Absorption ◽  
Structural Integrity ◽  
Somatostatin Analogue ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Solid Dosage Forms ◽  
Intestinal Tissue ◽  
Solid Dosage ◽  
Sprague Dawley Rats

Acylcarnitines were tested as potential absorption-enhancing agents for drugs that are poorly absorbed from the gastrointestinal tract. Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested, although significant increases in drug absorption were observed with acylcarnitines containing C12 through C18 fatty acid chains. Palmitoyl-DL-carnitine afforded significant increases in the absorption of cefoxitin, gentamicin, cytarabine, somatostatin analogue, and alpha-methyldopa. The response to palmitoyl-DL-carnitine was concentration dependent and reversible within 60-120 min. Histological examination of the intestinal tissue revealed no apparent change in mucosal structural integrity at doses of palmitoyl-DL-carnitine that resulted in increased drug absorption. The acylcarnitines were effective in increasing drug absorption from the small intestine and the rectal compartment of both rats and dogs. The data also demonstrated effectiveness with aqueous and solid dosage forms (Witepsol H-15 suppositories). The data suggest that acylcarnitines may be effective and safe absorption-enhancing agents for a variety of drugs.

Intraneuronal accumulations of lysosomes in the cerebellum of rats and dogs after dosing with MDL-832

1990 ◽  
Vol 48 (3) ◽  
pp. 830-831
Author(s):  
S.D. Barnard ◽  
S.D. Warner
Keyword(s):  
Brown Pigment ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Gelatin Capsules ◽  
Pigment Granules ◽  
Sprague Dawley Rats ◽  
Hematoxylin And Eosin ◽  
Dose Levels

1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.

Inhibition of sucrose intake by continuous celiac, superior mesenteric, and intravenous CCK-8 infusions

1996 ◽  
Vol 270 (2) ◽  
pp. R319-R325 ◽  
Author(s):  
J. E. Cox ◽  
S. M. McCown ◽  
J. M. Bridges ◽  
W. J. Tyler
Keyword(s):  
Gastrointestinal Tract ◽  
Superior Mesenteric Artery ◽  
Mesenteric Artery ◽  
Jugular Vein ◽  
Sucrose Intake ◽  
Sprague Dawley ◽  
Cholecystokinin Octapeptide ◽  
Behavioral Observations ◽  
Sprague Dawley Rats ◽  
Abdominal Arteries

Two experiments compared the potency of continuous infusions of cholecystokinin octapeptide (CCK-8) for reducing sucrose intake when administered into abdominal arteries or the jugular vein. Adult, male Sprague-Dawley rats received 22-min infusions of saline or several doses of CCK-8. Sucrose was available for 20 min, beginning 2 min after onset of infusions. In the first experiment, intraceliac CCK-8 in doses of 50, 125, and 312 ng produced significant reductions in intake, but no dose affected intake when administered into the jugular vein. In experiment 2, only the highest dose, 312 ng, suppressed intake when infused into the superior mesenteric artery, and jugular infusions were again ineffective. Behavioral observations indicated that intra-arterial CCK-8 had no affect on feeding within the first several minutes of test meals but accelerated the subsequent decline in incidence of feeding. These results suggest that receptors involved in cholecystokinin satiety are widely distributed within the gastrointestinal tract.

Non-clinical safety and pharmacokinetic evaluations of propylene glycol aerosol in Sprague-Dawley rats and Beagle dogs

Toxicology ◽  
2011 ◽  
Vol 287 (1-3) ◽  
pp. 76-90 ◽  
Author(s):  
Michael S. Werley ◽  
Paddy McDonald ◽  
Patrick Lilly ◽  
Daniel Kirkpatrick ◽  
Jeffrey Wallery ◽  
...  
Keyword(s):  
Propylene Glycol ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Clinical Safety ◽  
Sprague Dawley Rats

scholarly journals Preclinical Toxicity Evaluation of Tepoxalin, a Dual Inhibitor of Cyclooxygenase and 5-Lipoxygenase, in Sprague—Dawley Rats and Beagle Dogs

1996 ◽  
Vol 33 (1) ◽  
pp. 38-48
Author(s):  
E. V. KNIGHT ◽  
J. P. KIMBALL ◽  
C. M. KEENAN ◽  
I. L. SMITH ◽  
F. A. WONG ◽  
...  
Keyword(s):  
Beagle Dogs ◽  
Sprague Dawley ◽  
Toxicity Evaluation ◽  
Dual Inhibitor ◽  
Sprague Dawley Rats

Pharmacokinetics in Sprague-Dawley rats and Beagle dogs andin vitrometabolism of ZJM-289, a novel nitric dioxide donor

Xenobiotica ◽  
2013 ◽  
Vol 44 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Ning Li ◽  
Zhixia Qiu ◽  
Xuliang Wang ◽  
Tingting Li ◽  
Hui Ji ◽  
...  
Keyword(s):  
Beagle Dogs ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Toxicity Profile of Artesunate in Rats and Dogs

2021 ◽  
Author(s):  
Johanna Susanne Lang
Keyword(s):  
Clinical Pathology ◽  
Toxicity Profile ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Respiratory Parameters ◽  
Safety Parameters ◽  
Repeated Administrations ◽  
Single Intravenous Administration ◽  
Intramuscular Artesunate

OBJECTIVES: The objectives of these studies were to investigate the toxicity, safety and toxicokinetics of single and multiple doses of artesunate for injection in rats and dogs. METHODS: Sprague-Dawley rats and Beagle dogs were treated intravenously or intramuscularly for 28 consecutive days with doses of up to 30 mg/kg artesunate, evaluating toxicity, kinetics, genotoxicity, and cardiovascular and central nervous safety parameters after single and 4-week repeated administrations. Furthermore, respiratory parameters were evaluated after a single intravenous administration in rats. RESULTS: Artesunate was well tolerated with no mortality and only minor effects on clinical pathology parameters. CONCLUSIONS: The results obtained in these studies support the safe use of intravenous and intramuscular artesunate in humans.

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