Systemic exposure to parabens: Pharmacokinetics, tissue distribution, excretion balance and plasma metabolites of [14C]-methyl-, propyl- and butylparaben in rats after oral, topical or subcutaneous administration

2012 ◽  
Vol 50 (3-4) ◽  
pp. 445-454 ◽  
Author(s):  
Nicolas Aubert ◽  
Thibault Ameller ◽  
Jean-Jacques Legrand
Keyword(s):  
Tissue Distribution ◽  
Subcutaneous Administration ◽  
Systemic Exposure ◽  
Plasma Metabolites ◽  
Excretion Balance

A long-term intravenous model of aluminum maltol toxicity in rabbits: Tissue distribution, hepatic, renal, and neuronal cytoskeletal changes associated with systemic exposure

1989 ◽  
Vol 98 (1) ◽  
pp. 58-74 ◽  
Author(s):  
Roger L. Bertholf ◽  
Mary M. Herman ◽  
John Savory ◽  
Richard M. Carpenter ◽  
Benjamin C. Sturgill ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Systemic Exposure

scholarly journals Effect of Water Extract of Mangosteen Pericarp on Donepezil Pharmacokinetics in Mice

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5246
Author(s):  
Mingoo Bae ◽  
Seung Yon Han ◽  
Eun-Sun Kim ◽  
Byung Hoon You ◽  
Young-Mi Kim ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Tissue Distribution ◽  
Neuroblastoma Cells ◽  
Water Extract ◽  
Systemic Exposure ◽  
Inhibitory Effect ◽  
Target Tissue ◽  
Herbal Products ◽  
The Brain ◽  
Memory Enhancing

The pharmacokinetic (PK) change in a drug by co-administered herbal products can alter the efficacy and toxicity. In the circumstances that herb–drug combinations have been increasingly attempted to alleviate Alzheimer’s disease (AD), the PK evaluation of herb–drug interaction (HDI) is necessary. The change in systemic exposure as well as target tissue distribution of the drug have been issued in HDIs. Recently, the memory-enhancing effects of water extract of mangosteen pericarp (WMP) has been reported, suggesting a potential for the combination of WMP and donepezil (DNP) for AD treatment. Thus, it was evaluated how WMP affects the PK change of donepezil, including systemic exposure and tissue distribution in mice after simultaneous oral administration of DNP with WMP. Firstly, co-treatment of WMP and donepezil showed a stronger inhibitory effect (by 23.0%) on the neurotoxicity induced by Aβ(25–35) in SH-SY5Y neuroblastoma cells than donepezil alone, suggesting that the combination of WMP and donepezil may be more effective in moderating neurotoxicity than donepezil alone. In PK interaction, WMP increased donepezil concentration in the brain at 4 h (by 63.6%) after administration without affecting systemic exposure of donepezil. Taken together, our results suggest that WMP might be used in combination with DNP as a therapy for AD.

Tissue distribution of ibogaine after intraperitoneal and subcutaneous administration

Life Sciences ◽  
1996 ◽  
Vol 58 (7) ◽  
pp. PL119-PL122 ◽  
Author(s):  
Lindsay B. Hough ◽  
Sandra M. Pearl ◽  
Stanley D. Glick
Keyword(s):  
Tissue Distribution ◽  
Subcutaneous Administration

scholarly journals Tissue distribution of emulsified γ-tocotrienol and its long-term biological effects after subcutaneous administration

2014 ◽  
Vol 13 (1) ◽  
pp. 66 ◽  
Author(s):  
Lili Deng ◽  
Ying Peng ◽  
Yu Wu ◽  
Meilin Yang ◽  
Yuedi Ding ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Biological Effects ◽  
Subcutaneous Administration

Pharmacokinetics, tissue distribution, and excretion of FGF-21 following subcutaneous administration in rats

2018 ◽  
Vol 10 (7) ◽  
pp. 1061-1069 ◽  
Author(s):  
Yufei He ◽  
Yazhuo Li ◽  
Zihong Wei ◽  
Xingyan Zhang ◽  
Jing Gao ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Subcutaneous Administration

scholarly journals Safety evaluation of the interchangeable use of robenacoxib in commercially-available tablets and solution for injection in cats

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Mark C. Heit ◽  
L. Jay Stallons ◽  
Wolfgang Seewald ◽  
Caryn M Thompson ◽  
Céline E. Toutain ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Day Treatment ◽  
Oral Treatment ◽  
Subcutaneous Administration ◽  
Systemic Exposure ◽  
Control Group ◽  
Serious Adverse Events ◽  
Blood Concentrations ◽  
Daily Dose

Abstract Background Robenacoxib (Onsior™) is a non-steroidal anti-inflammatory drug developed for canine and feline use for the control of pain and inflammation. It is available as both tablets and solution for injection. The objective of this study was to evaluate the safety of the interchangeable use of commercially available robenacoxib formulations when administered to cats orally using 6 mg tablets and subcutaneously using a solution for injection containing 20 mg/mL. Thirty-four naïve healthy 4-month old cats were enrolled in this 37-day study and were randomized to four groups (three robenacoxib and one control). One robenacoxib group received the maximum recommended dose (MRD) rate of each formulation, while the other two received two and three times this dose rate. The cats underwent three 10-day treatment cycles comprised of seven days of once daily oral administration followed by three days of subcutaneous administration. The third cycle was followed by an additional seven days of oral treatment. The control group received oral empty gelatin capsules or subcutaneous saline injections. Assessment of safety was based on general health observations, clinical observations, physical, ophthalmic, electrocardiographic and neurological examinations, clinical pathology evaluations, food consumption, body weight, and macroscopic and microscopic examinations. Blood samples were collected for toxicokinetic evaluation. Results Blood concentrations of robenacoxib confirmed systemic exposure of all treated cats. All cats were in good health through study termination and there were no serious adverse events during the study. There were no changes in body weight, food consumption, ophthalmic, physical or neurological examinations during the study. Treatment-related abnormalities were of low occurrence at all doses and included injection site changes (transient edema with minimal or mild, subacute/chronic inflammation histologically) and prolongation of the QT interval. These findings were consistent with previously observed findings in studies with robenacoxib administered separately orally or subcutaneously in cats. Thus, there were no adverse effects that could be attributed specifically to the interchangeable use of oral and injectable robenacoxib. Conclusions This 37-day laboratory study supports the safety of interchanging robenacoxib injection at a daily dose of 2 mg/kg with robenacoxib tablets at a daily dose of 1 mg/kg, or vice versa.

scholarly journals Vitamin K Tissue Distribution Is Modified by Large-Dose Warfarin and Menaquinone-4 Content of the Diet

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1800-1800
Author(s):  
Guylaine Ferland ◽  
Pierre Allaire ◽  
Bouchra Ouliass
Keyword(s):  
Adipose Tissue ◽  
Tissue Distribution ◽  
Large Dose ◽  
Subcutaneous Administration ◽  
Experimental Period ◽  
Group Differences ◽  
Funding Sources ◽  
Dose Warfarin ◽  
Male Wistar Rats ◽  
One Way Anova

Abstract Objectives Investigate the influence of large-dose warfarin (W) on tissue K1 and MK-4 distribution in rats fed a standard K1 diet, or enriched with MK4. Methods Male Wistar rats were fed a regular K1 (750 mcg K1/kg/diet; WK1) or enriched MK-4 (100 mg MK-4/kg/diet; WK1 + MK4) diet for 1 week after which they were administered 14 mg W/kg/day (in drinking water) and subcutaneous K1 (94 mg/kg, 3X/week; to maintain coagulation), for 12 weeks; diets were maintained throughout the experimental period. Respective diet controls (C and C + MK4) received subcutaneous saline and regular water. K1 and M-4 quinone and their epoxide forms (K1O and MK-4O) were assessed in serum, liver, heart, kidney, pancreas, adipose tissue and brain, by HPLC. Group differences were tested by one-way ANOVA, and by t-test for each K vitamer. Results In C group, K1 was the predominant K vitamer in serum, liver and heart, whereas MK-4 was found in relative higher concentrations in kidney, pancreas, brain, and adipose tissue. In MK-4 containing organs, W treatment was associated with significantly lower MK-4 concentration in pancreas, brain, and heart (P < 0.05) despite the local presence of K1, which suggests that W may block the production of MK-4 by UBIAD1. Compared to C group, K1 concentrations were significantly higher in all organs and serum in WK1 and WK1 + MK4 groups as a result of the subcutaneous administration. Interestingly, in WK1 animals who had received a MK-4 enriched diet (WK1 + MK4), K1 concentrations in naturally K1 rich tissues (i.e., liver, heart and serum) were significantly increased when compared to those from the WK1 group (P < 0.05), suggesting that dietary MK-4 may play a role in modulating the uptake of K1 in these tissues. Except in liver, W administration (WK1 and WK1 + MK4) was associated with higher tissue concentrations of K1 and MK-4 epoxide when compared to C group (P < 0.05). Noteworthy, in WK1 animals who had received a MK-4 enriched diet (WK1 + MK4), naturally rich MK-4 containing organs (i.e., kidney, pancreas, adipose tissue and brain) presented significantly higher concentration of MK-4 epoxide (relative to K1 epoxide), suggesting a preferential use of MK4 by these organs when available from the diet. Conclusions In conclusion, results from this study point to modulatory roles of W and dietary MK-4 on tissue distribution of K1 and MK-4 in what appears to be a tissue specific manner. Funding Sources CIHR.

Comparison of systemic exposure to nemifitide following two methods of subcutaneous administration to healthy volunteers

2005 ◽  
Vol 26 (9) ◽  
pp. 379-385 ◽  
Author(s):  
G. Nicolau ◽  
J.P. Feighner ◽  
R. Stout ◽  
J. Hlavka ◽  
M. Gutierrez ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Subcutaneous Administration ◽  
Systemic Exposure

scholarly journals Kinetics of Tissue Distribution and Elimination of Pyrene and 1-Hydroxypyrene Following Intravenous Administration of [14C]Pyrene in Rats

1998 ◽  
Vol 46 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Michéle Bouchard ◽  
Kannan Krishnan ◽  
Claude Viau
Keyword(s):  
Tissue Distribution ◽  
Systemic Exposure ◽  
The Body ◽  
Terminal Phase ◽  
Gi Tract ◽  
Elimination Phase ◽  
First Order ◽  
T Values ◽  
Kinetics Of ◽  
Terminal Elimination Phase

Abstract The tissue distribution and elimination of pyrene and 1-hydroxy-pyrene (1-OHP) were evaluated in male Sprague-Dawley rats (210–240 g) following an intravenous injection of 50 μmol/kg of [14C]pyrene. Blood and tissues were removed and urine and feces were collected at 1, 2, 4, 8, 16, and 24 h postdosing. [14C]Pyrene equivalents were measured by liquid scintillation counting, and β-glucuronidase/arylsulfatase-treated blood, tissues, and excreta were analyzed for pyrene and 1-OHP by HPLC/fluorescence. At 1 h, the largest fraction of the dose was found in adipose tissue, essentially as pyrene, and its elimination followed first-order monophasic kinetics with a half-life (t½) of 4.9 h. In blood, liver, kidney, lung, muscle, and gastrointestinal (GI) tract, kinetics of [14C]pyrene equivalents were biphasic and average t½ values for the terminal elimination phase (8 to 24 h) ranged between 6.2 and 8.7 h. Elimination of pyrene in blood and these tissues except the GI tract followed first-order biphasic kinetics with average t½ values of the terminal phase ranging between 3.6 and 5.4 h. In the GI tract, a monophasic elimination kinetics of pyrene was observed with mean t½ value of 3.1 h. Kinetics of 1-OHP in blood and liver showed a monophasic elimination with mean t½ values of 6.7 and 6.2 h, respectively. Kinetics of 1-OHP in the other tissues were biphasic with average t½ values of the terminal elimination phase ranging between 5.2 and 6.2 h. At 24 h, on average, 81.7% of the dose was recovered in the urine (57.2%), feces (18.3%), and GI tract (6.2%) as [14C]pyrene equivalents with 2.7 and 1.9% of dose excreted as total 1-OHP in urine and feces, respectively. At all time points, 1-OHP in urine represented a constant fraction of total 14C in urine and feces. These results indicate that (i) [14C]pyrene was rapidly distributed, metabolized, and eliminated from the body, and (ii) although 1-OHP represents a small percentage of total pyrene eliminated from the body, it remains a reliable indicator of systemic exposure to, and overall elimination of the 14C associated with, this polycyclic aromatic hydrocarbon.

scholarly journals Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans

2021 ◽  
Vol 14 (8) ◽  
pp. 830
Author(s):  
Hyewon Chung ◽  
Jin-Woo Park ◽  
Dai-Hyun Kim ◽  
Soo-Hong Seo ◽  
Kyoung-Ah Kim ◽  
...  
Keyword(s):  
Cholic Acid ◽  
Deoxycholic Acid ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Systemic Exposure ◽  
Blood Lipid ◽  
Pharmacokinetic Analysis ◽  
Post Dose ◽  
Before And After

This study aimed to explore pharmacokinetics, pharmacodynamics, and safety/tolerability of MT921, an injectable cholic acid, after a single subcutaneous administration to healthy volunteers. A randomized, double-blinded, placebo-controlled, single dose-ascending phase 1 study enrolled 24 subjects who were assigned to three groups (60 mg, 120 mg, and 150 mg) of MT921. Blood samples were obtained for a 24-h period before and after injecting MT921 to the submental fat area. Plasma concentrations of cholic acid and deoxycholic acid were determined for pharmacokinetic analysis. Levels of free fatty acid, triglyceride, and total cholesterol were measured for pharmacodynamic analysis. Safety and tolerability were assessed until 21 days post-dose. While systemic exposure to cholic acid tended to increase as the MT921 dose increased, pharmacokinetic profiles of deoxycholic acid were similar among dose groups without showing significant changes. Pharmacodynamic profiles were comparable when measured at baseline and post-dose. The most frequent adverse events were injection site pain and edema. All adverse drug reactions resolved without treatment. MT921 appeared to be well-tolerated after an injection to the submental area at a dose up to 150 mg. Systemic exposure to cholic acid increased as the dose increased. Blood lipid profiles and deoxycholic acid levels were not affected by MT921 treatment.

Sign in / Sign up

Export Citation Format

Share Document