scholarly journals Absorption, Metabolism, and Excretion by Freely Moving Rats of 3,4-DHPEA-EDA and Related Polyphenols from Olive Fruits (Olea europaea)

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Shunsuke Kano ◽  
Haruna Komada ◽  
Lina Yonekura ◽  
Akihiko Sato ◽  
Hisashi Nishiwaki ◽  
...  
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Homovanillic Acid ◽  
Biological Activities ◽  
Parent Compound ◽  
Area Under The Curve ◽  
Bioactive Compound ◽  
Freely Moving Rats ◽  
Portal Plasma ◽  
Freely Moving

Absorption, metabolism, and excretion of 3,4-DHPEA-EDA, oleuropein, and hydroxytyrosol isolated from olive fruits were newly evaluated after oral and intravenous administration in freely moving rats cannulated in the portal vein, jugular vein, and bile duct. Orally administered 3,4-DHPEA-EDA, an important bioactive compound in olive pomace, was readily absorbed and metabolized to hydroxytyrosol, homovanillic acid, and homovanillyl alcohol, as shown by dose-normalized 4 h area under the curve (AUC0→4 h/Dose) values of 27.7, 4.5, and 4.2 μM·min·kg/μmol, respectively, in portal plasma after oral administration. The parent compound 3,4-DHPEA-EDA was not observed in the portal plasma, urine, and bile after oral and intravenous administration. Additionally, hydroxytyrosol, homovanillic acid, and homovanillyl alcohol in the portal plasma after oral administration of hydroxytyrosol showed 51.1, 22.8, and 7.1 μM·min·kg/μmolAUC0→4 h/Dose, respectively. When oleuropein, a polar glucoside, was injected orally, oleuropein in the portal plasma showed 0.9 μM·min·kg/μmolAUC0→4 h/Dose. However, homovanillic acid was detected from oleuropein in only a small amount in the portal plasma. Moreover, the bioavailability of hydroxytyrosol and oleuropein for 4 hours was 13.1% and 0.5%, respectively. Because the amount of 3,4-DHPEA-EDA in olive fruits is about 2-3 times greater than that of hydroxytyrosol, the metabolites of 3,4-DHPEA-EDA will influence biological activities.

Intravenous administration of inorganic selenium compounds, inhibitors of prostaglandin D synthase, inhibits sleep in freely moving rats

1993 ◽  
Vol 623 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Ryuichi Takahata ◽  
Hitoshi Matsumura ◽  
Sachi Sri Kantha ◽  
Etsuko Kubo ◽  
Kumiko Kawase ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Selenium Compounds ◽  
Freely Moving Rats ◽  
Inorganic Selenium ◽  
Prostaglandin D Synthase ◽  
Freely Moving

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 Orexin A suppresses in vivo GH secretion

2004 ◽  
pp. 731-736 ◽  
Author(s):  
LM Seoane ◽  
SA Tovar ◽  
D Perez ◽  
F Mallo ◽  
M Lopez ◽  
...  
Keyword(s):  
Nutritional Status ◽  
Area Under The Curve ◽  
Sleep Regulation ◽  
Gh Secretion ◽  
Neuroendocrine Function ◽  
Freely Moving Rats ◽  
Freely Moving ◽  
The Brain

BACKGROUND/AIMS: Orexins (OXs) are a newly described family of hypothalamic neuropeptides. Based on the distribution of OX neurons and their receptors in the brain, it has been postulated that they could play a role in the regulation of neuroendocrine function. GH secretion is markedly influenced by nutritional status and body weight. To investigate the role OX-A plays in the neuroregulation of GH secretion we have studied its effect on spontaneous GH secretion as well as GH responses to GHRH and ghrelin in freely moving rats. Finally, we also assessed the effect of OX-A on in vitro GH secretion. METHODS: We administered OX-A (10 microg, i.c.v.) or vehicle (10 microl, i.c.v.) to freely moving rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. RESULTS: Administration of OX-A led to a decrease in spontaneous GH secretion in comparison with vehicle-treated rats, as assessed by mean GH levels (means+/-s.e.m. 4.2+/-1.7 ng/ml vs 9.4+/-2.2 ng/ml; P<0.05), mean GH amplitude (3.6+/-0.5 ng/ml vs 20.8+/-5.6 ng/ml; P<0.01) and area under the curve (848+/-379 ng/ml per 4 h vs 1957+/-458 ng/ml per 4 h; P<0.05). In contrast, OX-A failed to modify in vivo GH responses to GHRH (10 microg/kg, i.v.) although it markedly blunted GH responses to ghrelin (40 microg/kg, i.v.) (mean peak GH levels: 331+/-71 ng/ml, vehicle, vs 43+/-11 ng/ml in OX-A-treated rats; P<0.01). Finally, OX-A infusion (10(-7), 10(-8) or 10(-9) M) failed to modify in vitro basal GH secretion or GH responses to GHRH, ghrelin and KCl. CONCLUSIONS: These data indicate that OX-A plays an inhibitory role in GH secretion and may act as a bridge among the regulatory signals that are involved in the control of growth, nutritional status and sleep regulation.

scholarly journals Effect of oral administration of zanapezil (TAK-147) for 21 days on acetylcholine and monoamines levels in the ventral hippocampus of freely moving rats

2005 ◽  
Vol 145 (8) ◽  
pp. 1035-1044 ◽  
Author(s):  
Izzettin Hatip-Al-Khatib ◽  
Katsunori Iwasaki ◽  
Yoshitaka Yoshimitsu ◽  
Takashi Arai ◽  
Nobuaki Egashira ◽  
...  
Keyword(s):  
Oral Administration ◽  
Ventral Hippocampus ◽  
Freely Moving Rats ◽  
Freely Moving
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