Rapid evaluation of rumen protection status of orally administered DL-methionine mixes using an HPLC analysis of plasma methionine

1991 ◽  
Vol 31 (3) ◽  
pp. 315 ◽  
Author(s):  
RGA Stephenson ◽  
L PalmerC ◽  
GR Suter
Keyword(s):  
Oral Administration ◽  
Protein Hydrolysate ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Positive Control ◽  
Bacterial Degradation ◽  
Laboratory Evaluation ◽  
Wool Growth ◽  
Head Level

The measurement of plasma methionine concentrations with high pressure liquid chromatography (HPLC) with a protein hydrolysate column was examined as a means of evaluating the rumen protection status of DL-methionine mixes after oral administration. Plasma methionine concentrations were measured 2, 4, 6 and 8 h after 5 different mixes had been administered to the rumen of 3 sheep by stomach tube. The plasma values were compared with the pretreatment profile (1.2-16.7 �mol/L) obtained in the test sheep, and those obtained after abomasal and subcutaneous administration. The results suggest that none of the mixes were significantly protected from bacterial degradation in the rumen. The positive control treatments of subcutaneous or abomasal administration resulted in >10-fold increases in plasma concentrations of methionine (e.g. from 28 to 414 �mol/L). A method of administration that required the sheep to raise their heads about 30 cm to lick a molasses + methionine mix increased subsequent plasma methionine concentrations 5 times (from 44 to 267 �mol/L). Oral administration of 2 mixes using a drench gun also resulted in increased plasma methionine in some sheep, suggesting that these procedures allowed some methionine to bypass the rumen mechanically. A follow-on wool growth experiment using methionine + molasses mixes administered either from a 'licker' 30 cm above head level or in the feedbin failed to increase either wool growth or plasma methionine. The HPLC procedure for methionine analysis proved successful for the qualitative laboratory evaluation of the rumen protection status of methionine mixes. It is concluded that this 24 h methionine test and analysis procedure can partly replace the costly and lengthy in vivo procedure of measuring responses in wool production.

scholarly journals Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats

2020 ◽  
Vol 13 (9) ◽  
pp. 231
Author(s):  
Seung-Hyun Jeong ◽  
Ji-Hun Jang ◽  
Yong-Bok Lee
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Phase ◽  
Routes Of Administration ◽  
Administration Routes ◽  
Pharmacokinetic Profiles

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.

scholarly journals Pharmacokinetics of Doxycycline in Adults with Cystic Fibrosis

2011 ◽  
Vol 56 (1) ◽  
pp. 70-74 ◽  
Author(s):  
Paul M. Beringer ◽  
Heather Owens ◽  
Albert Nguyen ◽  
Debbie Benitez ◽  
Adupa Rao ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Oral Administration ◽  
Maximum Concentration ◽  
Airway Remodeling ◽  
Plasma Concentrations ◽  
Compartment Model ◽  
Time Curve ◽  
Elimination Half ◽  
Dose Oral

ABSTRACTCystic fibrosis (CF) is characterized by a chronic neutrophilic inflammatory response resulting in airway remodeling and progressive loss of lung function. Doxycycline is a tetracycline antibiotic that inhibits matrix metalloproteinase 9, a protease known to be associated with the severity of lung disease in CF. The pharmacokinetics of doxycycline was investigated during the course of a clinical trial to evaluate the short-term efficacy and safety in adults with CF. Plasma samples were obtained from 14 patients following a single intravenous dose and after 2 and 4 weeks of oral administration of doses ranging from 40 to 200 mg daily. The data were analyzed using noncompartmental and compartmental pharmacokinetics. The maximum concentration of drug in serum (Cmax) and area under the concentration-time curve from 0 h to infinity (AUC0-∞) values ranged from 1.0 to 3.16 mg/liter and 15.2 to 47.8 mg/liter × h, respectively, following single intravenous doses of 40 to 200 mg.Cmaxand time to maximum concentration of drug in serum (Tmax) values following multiple-dose oral administration ranged from 1.15 to 3.04 mg/liter and 1.50 to 2.33 h, respectively, on day 14 and 1.48 to 3.57 mg/liter and 1.00 to 2.17 on day 28. Predose sputum/plasma concentration ratios on days 14 and 28 ranged from 0.33 to 1.1 (mean, 0.71 ± 0.33), indicating moderate pulmonary penetration. A 2-compartment model best described the combined intravenous and oral data. Absorption was slow and delayed (absorption rate constant [Ka], 0.414 h−1; lag time, 0.484 h) but complete (bioavailability [F], 1.16). The distribution and elimination half-lives were 0.557 and 18.1 h, respectively. Based on these data, the plasma concentrations at the highest dose, 200 mg/day, are in the range reported to produce anti-inflammatory effectsin vivoand should be evaluated in clinical trials.

Abstract 034: Characterization of A Novel Maternally Restricted Pro-angiogenic Therapeutic for Preeclampsia

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
William H Stewart ◽  
Eric George ◽  
Gene L Bidwell ◽  
Heather Chapman ◽  
Fakhri Mahdi ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Half Life ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Chronic Administration ◽  
Health Concern ◽  
Pathogenic Factors ◽  
Clearance Kinetics

Background: Preeclampsia is a major obstetrical health concern, affecting 5-8% of all pregnancies. Hallmarked by hypertension and endothelial dysfunction the origin of the disease remains obscure, though it is generally accepted that placental insufficiency/ischemia is a central cause. In response, the placenta secretes pathogenic factors, in particular the anti-angiogenic protein sFlt-1. Currently, there is no effective therapy for the management of the preeclampsia patient. We have recently produced a novel synthetic peptide based on placental growth factor (PlGF) which is maternally restricted by fusion to the synthetic carrier elastin like polypeptide (ELP). Here, we describe its in vivo pharmacokinetics and biodistribution. Methods: Fluorescently labeled ELP-PLGF was administered i.v. and blood sampled serially to determine clearance kinetics. Long-term pharmacokinetics and biodistribution was performed after subcutaneous administration of labeled peptide. Measurements were made on serially drawn blood, and in the whole animal by in vivo imaging. Results: ELP-PlGF exhibited markedly more favorable pharmacokinetics than the normal half life of PlGF, with a terminal half-life of ~10 hours as opposed to ~30 minutes for PlGF alone. Chronic administration found highest levels accumulating in placenta and kidney (two favorable targets for preeclampsia) and liver. A single subcutaneous administration at 100mg/kg resulted in sustained therapeutic plasma concentrations for over 10 days. Conclusion: These data demonstrate that ELP-PlGF has favorable pharmacokinetic and biodistribution profiles. Previous data suggest ELP-PlGF directly antagonizes sFlt-1 in culture. Future studies to assess the in vivo effectiveness of ELP-PlGF in managing placental ischemia induced hypertension and endothelial dysfunction are currently in progress. Acknowledgment: This work was supported by NIH grants R0121527 (GLB), T32HL105324 (OCL), P01HL51971, P20GM104357 (EMG), and R00HL116774 (EMG)

scholarly journals Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Rosario Russo ◽  
Angelo Mancinelli ◽  
Michele Ciccone ◽  
Fabio Terruzzi ◽  
Claudio Pisano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sprague Dawley ◽  
Time Curve ◽  
Maximum Plasma Drug Concentration

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (μSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t1/2), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with μSMIN Plus™ compared with animals treated with micronized diosmin. In particular, μSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for μSMIN Plus™, which may represent a new tool for CVI management.

scholarly journals Characterization of PCL and Chitosan Nanoparticles as Carriers of Enoxaparin and Its Antithrombotic Effect in Animal Models of Venous Thrombosis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lucas Bessa Prado ◽  
Stephany Cares Huber ◽  
Aline Barnabé ◽  
Fernanda Dutra Santiago Bassora ◽  
Devanira Souza Paixão ◽  
...  
Keyword(s):  
Oral Administration ◽  
Encapsulation Efficiency ◽  
Anticoagulant Activity ◽  
Chitosan Nanoparticles ◽  
Subcutaneous Administration ◽  
Double Emulsion ◽  
In Vivo Studies ◽  
Control Group ◽  
Antithrombotic Effect

This study was based on the preparation, characterization, and animal in vivo experiments performed to evaluate nanoparticles of poly(ɛ-caprolactone) (PCL) and chitosan as carriers of enoxaparin. The nanoparticles were characterized and presented satisfactory results in terms of size, polydispersity, and encapsulation efficiency. Anticoagulant activity of the nanoparticles was maintained for 14 hours when the administration was subcutaneous; however no activity was observed after oral administration. There was a significant reduction in thrombus size, in vivo, for both free and encapsulated enoxaparin in comparison with the control group after subcutaneous administration. Oral administration results however were indifferent. In conclusion, the double emulsion method w/o/w was efficient for enoxaparin encapsulation, producing spherical nanoparticles with high encapsulation efficiency. For in vivo studies, the encapsulated enoxaparin showed a sustained anticoagulant activity for a higher period of time compared to free enoxaparin, with an antithrombotic effect when administered subcutaneously.

scholarly journals Pharmacokinetics and Pharmacodynamics of Fosfomycin and Its Activity against Extended-Spectrum-β-Lactamase-, Plasmid-Mediated AmpC-, and Carbapenemase-ProducingEscherichia coliin a Murine Urinary Tract Infection Model

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Ilya Nikolaevich Zykov ◽  
Ørjan Samuelsen ◽  
Lotte Jakobsen ◽  
Lars Småbrekke ◽  
Dan I. Andersson ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Clinical Strain ◽  
Infection Model ◽  
Time Curve ◽  
Content Type ◽  
Tract Infections

ABSTRACTFosfomycin has become an attractive treatment alternative for urinary tract infections (UTIs) due to increasing multidrug resistance (MDR) inEscherichia coli. In this study, we evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) indices of fosfomycin and itsin vivoactivity in an experimental murine model of ascending UTI. Subcutaneous administration of fosfomycin showed that the mean peak plasma concentrations of fosfomycin were 36, 280, and 750 mg/liter following administration of a single dose of 0.75, 7.5, and 30 mg/mouse, respectively, with an elimination half-life of 28 min, and urine peak concentrations of 1,100, 33,400, and 70,000 mg/liter expected to be sustained above 1 mg/liter (MIC of the test strain, NU14) for 5, 8, and 9.5 h, respectively. The optimal PK/PD indices for reducing urine colony counts (number of CFU per milliliter) were determined to be the area under the concentration-time curve/MIC from 0 to 72 h and the maximum concentration/MIC on the basis of the dose-dependent bloodstream PK and the results of an evaluation of six dosing regimens. With a dosing regimen of 15 mg/mouse twice (every 36 h), fosfomycin significantly reduced the number of CFU per milliliter of all susceptible strains in urine, including clinical MDR strains, except for one clinical strain (P= 0.062). Variable degrees of reduction were observed in the bladder and kidneys. No significant reductions in the number of CFU per milliliter were observed with the resistant strains. In conclusion, fosfomycin shows concentration-dependentin vivoactivity, and the results suggest that fosfomycin is an effective alternative to carbapenems in treating MDRE. coliin uncomplicated UTIs. The data on the effectiveness of fosfomycin against the MDR isolates along with the results of PK/PD modeling should facilitate the further development of improved recommendations for its clinical use.

Studies of wool growth responses to 2-hydroxy-4-(methylthio) butanoic acid, Alimet, an analogue of methionine

1990 ◽  
Vol 30 (4) ◽  
pp. 477
Author(s):  
RGA Stephenson ◽  
GR Suter ◽  
DA Pritchard ◽  
MDJ Martin
Keyword(s):  
Growth Rate ◽  
Drinking Water ◽  
Plasma Concentrations ◽  
Growth Responses ◽  
Butanoic Acid ◽  
Merino Sheep ◽  
Wool Production ◽  
Wool Growth ◽  
Dry Seasons

An analogue of DL-methionine, Alimet, was evaluated for its commercial potential for increasing wool growth in Merino sheep in pen and grazing experiments. This was done by administering Alimet as a drench, in drinking water, or via rumen or abomasal fistula, and measuring wool growth rate and plasma methionine concentrations. In vivo data indicated that significant wool growth responses (23-35%) to Alimet as a drench or in drinking water occurred at low rates (estimated 5-6 g/sheep.day) of basal wool production when sheep were fed a lucerne diet to maintain liveweight. At higher rates of clean wool growth (10-12 g/sheep.day) when sheep were eating above-maintenance diets (lucerne ration or pasture), Alimet treatment was associated with variable and reduced response. A significant (P<0.05) negative correlation (r2 = 0.699, n = 11) between wool growth responses (x � s.d. = 0.11 � 0.067) to the 3 mL dose rate of Alimet and wool growth in control treatments (y �: s.d. = 0.70 � 0.202) confirmed the above trend. Four hours after administration of Alimet via either rumen or abomasal fistula, comparative plasma concentrations of methionine, 28 and 168 �mol/L respectively, suggest that Alimet is susceptible to degradation in the rumen. The corresponding values for DL-methionine, via either rumen or abomasal fistula, were 64 and 350 �mol/L, respectively. The small rises (40%) in plasma methionine values associated with significant increases in wool production indicate that a dose of 3 mL is as effective as 4 mL of Alimet when the basal nutritional regime is limiting. While administration of Alimet in drinking water during dry seasons is possible, the profitability of supplementation would need to be tested further.

scholarly journals Topiramate is more effective than acetazolamide at lowering intracranial pressure

Cephalalgia ◽  
2018 ◽  
Vol 39 (2) ◽  
pp. 209-218 ◽  
Author(s):  
William J Scotton ◽  
Hannah F Botfield ◽  
Connar SJ Westgate ◽  
James L Mitchell ◽  
Andreas Yiangou ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Oral Administration ◽  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Subcutaneous Administration ◽  
Female Rats ◽  
In Vivo Studies ◽  
Human Dose ◽  
High Doses

Background The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats. Methods We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate. Results At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% ( p = 0.0009) and 21% ( p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% ( p = 0.018), compared to 5% reduction with acetazolamide ( p = >0.999). Conclusion Our in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.

Endocrinological effects of single daily ketoconazole administration in male beagle dogs

1984 ◽  
Vol 107 (2) ◽  
pp. 275-281 ◽  
Author(s):  
Roland De Coster ◽  
Dominiek Beerens ◽  
Jef Dom ◽  
Gustaaf Willemsens
Keyword(s):  
Oral Administration ◽  
Plasma Cortisol ◽  
Plasma Concentrations ◽  
The Other ◽  
Plasma Testosterone ◽  
Beagle Dogs ◽  
Basal Cortisol ◽  
High Doses ◽  
Daily Oral Administration

Abstract. Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3–4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17α-hydroxyprogesterone, progesterone and 17α,20α-dihydroxyprogesterone increased within 3–10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17α levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17–20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17β plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.

scholarly journals Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 71 ◽  
Author(s):  
Yu-Feng Yao ◽  
Chao-Zhan Lin ◽  
Fang-Le Liu ◽  
Run-Jing Zhang ◽  
Qiu-Yu Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Time Curve ◽  
Tof Ms

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

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