scholarly journals Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262336
Author(s):  
Jennifer M. Reinhart ◽  
Gabriela A. R. de Oliveira ◽  
Lauren Forsythe ◽  
Zhong Li
Keyword(s):  
Therapeutic Range ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Good Manufacturing Practice ◽  
Liquid Chromatography Mass Spectrometry ◽  
Plasma Theophylline ◽  
Serial Blood Sampling ◽  
Healthy Dogs ◽  
Steady State Predictions ◽  
Important Drug

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 μg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 μg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.

scholarly journals Targeted metabolomics as a tool in discriminating endocrine from primary hypertension

2020 ◽  
Author(s):  
Zoran Erlic ◽  
Parminder Reel ◽  
Smarti Reel ◽  
Laurence Amar ◽  
Alessio Pecori ◽  
...  
Keyword(s):  
Multivariate Analyses ◽  
Cushing Syndrome ◽  
Area Under The Curve ◽  
Primary Hypertension ◽  
Liquid Chromatography Mass Spectrometry ◽  
Targeted Metabolomics ◽  
Metabolic Pattern ◽  
Machine Learning Approach ◽  
Arginine Aspartate ◽  
Stored Blood

Abstract Context Identification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL] and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and endocrine conditions associated with hypertension. Objective Use TM to identify distinct metabolic patterns between primary hypertension (PHT) and EHT and test its discriminating ability. Design Retrospective analyses of PHT and EHT patients from a European multicentre study (ENSAT-HT). TM was performed on stored blood samples using liquid chromatography mass spectrometry. To identify discriminating metabolites a “classical approach” (CA) (performing a series of univariate and multivariate analyses) and a “machine learning approach” (MLA) (using Random Forest) were used. Patients The study included 282 adult patients (52% female; mean age 49 years) with proven PHT (n=59) and EHT (n=223 with 40 CS, 107 PA and 76 PPGL), respectively. Results From 155 metabolites eligible for statistical analyses, 31 were identified discriminating between PHT and EHT using the CA and 27 using the MLA, of which 15 metabolites (C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC16:0, lysoPCaC20:4, lysoPCaC24:0, PCaeC42:0, SM C18:1, SM C20:2) were found by both approaches. The ROC curve built on the top 15 metabolites from the CA provided an area under the curve (AUC) of 0.86, which was similar to the performance of the 15 metabolites from MLA (AUC 0.83). Conclusions TM identifies distinct metabolic pattern between PHT and EHT providing promising discriminating performance.

scholarly journals Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Anthony D. Kang ◽  
Kenneth P. Smith ◽  
Anders H. Berg ◽  
Katherine A. Truelson ◽  
George M. Eliopoulos ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Gram Negative ◽  
Content Type ◽  
Model Treatment

ABSTRACT Apramycin, an aminocyclitol aminoglycoside, was rapidly bactericidal against Acinetobacter baumannii . In a neutropenic murine thigh infection model, treatment-associated A. baumannii CFU reductions of >4 log 10 per thigh were observed for all exposures for which area under the curve (AUC)/MIC ratio was >50 and maximum concentration of drug in serum ( C max )/MIC was ≈10 or higher. Based on these findings, we suggest that apramycin deserves further preclinical exploration as a repurposed therapeutic for multidrug-resistant Gram-negative pathogens, including A. baumannii .

scholarly journals Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 832 ◽  
Author(s):  
Kelly A. Deabold ◽  
Wayne S. Schwark ◽  
Lisa Wolf ◽  
Joseph J. Wakshlag
Keyword(s):  
Single Dose ◽  
Adverse Effects ◽  
Safety Data ◽  
Area Under The Curve ◽  
Pet Owners ◽  
Dose Oral ◽  
Oral Pharmacokinetics ◽  
Healthy Dogs ◽  
Clinically Significant

The use of CBD-rich hemp products is becoming popular among pet owners with no long-term safety data related to consumption in adult dogs and cats. The purpose of this study was to determine the single-dose oral pharmacokinetics of CBD, and to provide a preliminary assessment of safety and adverse effects during 12-week administration using a hemp-based product in healthy dogs and cats. Eight of each species were provided a 2 mg/kg total CBD concentration orally twice daily for 12 weeks with screening of single-dose pharmacokinetics in six of each species. Pharmacokinetics revealed a mean maximum concentration (Cmax) of 301 ng/mL and 43 ng/mL, area under the curve (AUC) of 1297 ng-h/mL and 164 ng-h/mL, and time to maximal concentration (Tmax) of 1.4 h and 2 h, for dogs and cats, respectively. Serum chemistry and CBC results showed no clinically significant alterations, however one cat showed a persistent rise in alanine aminotransferase (ALT) above the reference range for the duration of the trial. In healthy dogs and cats, an oral CBD-rich hemp supplement administered every 12 h was not detrimental based on CBC or biochemistry values. Cats do appear to absorb or eliminate CBD differently than dogs, showing lower serum concentrations and adverse effects of excessive licking and head-shaking during oil administration.

scholarly journals PHARMACOKINETIC STUDIES OF A CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEM OF LORNOXICAM BY LC-MS/MS METHOD

2018 ◽  
Vol 10 (6) ◽  
pp. 88
Author(s):  
Sindhu Abraham ◽  
Rajamanickam Deveswaran ◽  
Jayaraman Anbu ◽  
Sharon Furtado ◽  
Bharath Srinivasan
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Immediate Release ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Half ◽  
Coated Tablet ◽  
Liquid Chromatography Tandem Mass

Objective: The objective of this study was to investigate differences in pharmacokinetic patterns of immediate release tablet (IR) and compression coated tablet (CCT) of lornoxicam, proposed for the chronotherapeutic treatment of rheumatoid arthritis.Methods: The dosage forms were administered to two groups of white New Zealand rabbits (n=3), and the plasma drug levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters like maximum concentration (Cmax), time is taken to reach maximum concentration (Tmax), area under the curve (AUC), elimination half-life (t1/2) and Mean Residence Time (MRT) were determined.Results: In the case of IR tablets, the drug was detected within 15 min after oral administration and a Cmax of 1269.57±4.04 ng/ml were attained at 2±0.15 h. With CCT, the drug was detected only after 5 h and a Cmax of 1279.24±12.76 ng/ml were attained at 8±0.10 h. The CCT showed maximum drug release at the eighth hour in comparison to IR tablet which showed maximum release at the second hour of study.Conclusion: The predominant lag time prior to drug release from CCT is an indication that it is consistent with the requirements of chronopharmaceutical drug delivery. The results suggest that the compression coated tablet is a promising approach for chronotherapeutic management of rheumatoid arthritis.

scholarly journals Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1190
Author(s):  
David Briskey ◽  
Amanda Rao
Keyword(s):  
Single Dose ◽  
Oral Bioavailability ◽  
Maximum Concentration ◽  
Randomized Study ◽  
Venous Blood ◽  
Area Under The Curve ◽  
Fold Increase ◽  
Double Blind ◽  
Potential Health ◽  
Liquid Chromatography Tandem Mass

Resveratrol is a naturally produced compound that has been well researched for its potential health benefits. The primary hindrance towards resveratrol’s therapeutic efficacy is its traditionally poor oral bioavailability. LipiSperse® is a novel delivery system designed to increase the dispersion of lipophilic ingredients, like resveratrol, in aqueous environments. This single-dose, double-blind, randomized study compared the pharmacokinetics of a commercially available resveratrol with (Veri-Sperse®) and without (Veri-te) the LipiSperse® delivery complex. Healthy adults randomly received a single dose of either 150 Veri-te, 75 Veri-Sperse®, or 150 mg Veri-Sperse®. Venous blood samples were taken prior to dosing in a fasted state and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 h post supplementation. Plasma trans-resveratrol conjugates were measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The area under the curve (AUC) (0–24 h), maximum concentration (Cmax), and time of maximum concentration (Tmax) of plasma conjugates were calculated. The 150 mg dose of Veri-Sperse® had a 2-fold increase in absorption (AUC) and a 3-fold increase in Cmax of trans-resveratrol conjugates compared to 150 mg Veri-te. There was no statistical difference between 75 Veri-Sperse and 150 mg Veri-te for AUC or Cmax of resveratrol conjugates. These findings provide support for the use of LipiSperse® to improve absorption of resveratrol.

Bioavailability of aspirin and salicylamide following oral co-administration in human volunteers

1991 ◽  
Vol 69 (10) ◽  
pp. 1436-1442 ◽  
Author(s):  
Mohamed S. Abdel-Rahman ◽  
Alluru S. Reddi ◽  
Frederick A. Curro ◽  
Rita M. Turkall ◽  
Abdelrazak M. Kadry ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Plasma Levels ◽  
Maximum Concentration ◽  
Peak Concentration ◽  
Area Under The Curve ◽  
Active Ingredients ◽  
Time Curve ◽  
Human Volunteers ◽  
Kinetics Of ◽  
Peak Value

BC® powder (I) is a commercially available analgesic containing the active ingredients aspirin and salicylamide. The kinetics of I, BC® powder minus aspirin (II), and BC® powder minus salicylamide (III) were evaluated in 13 volunteers. Ten minutes after administration of I, aspirin reached a maximum concentration of 12.9 μg/mL, while salicylamide concentration reached a peak value of 3.4 μg/mL. However, when III was administered, aspirin was not detected at 10 min and only reached a concentration of 0.4 μg/mL at 2 and 6 h. Furthermore, the area under the plasma concentration versus time curve for aspirin when III was administered was sixfold less compared with treatment with I. The area under the curve for aspirin metabolites was significantly different in I versus III. After treatment with II, a delay in salicylamide peak concentration was observed. Gentisamide was not detected throughout the study. This study demonstrates that salicylamide significantly enhances plasma levels of aspirin with potential therapeutic implications.Key words: aspirin, BC® powder, bioavailability, salicylamide.

Relative bioequivalence of amoxicillin dissolved in breast milk

2013 ◽  
Vol 99 (3) ◽  
pp. 258-261
Author(s):  
Parvaneh Yazdani-Brojeni ◽  
Facundo Garcia-Bournissen ◽  
Hisaki Fujii ◽  
Reo Tanoshima ◽  
Shinya Ito
Keyword(s):  
Breast Milk ◽  
Human Milk ◽  
Healthy Adult ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Fasting State ◽  
Oral Antibiotics ◽  
Liquid Chromatography Mass Spectrometry ◽  
Antibiotics Use ◽  
Adult Volunteers

BackgroundOral antibiotics use in infants in developing countries is challenging because liquid formulations are often unavailable. However, dissolving solid formulation of drugs in water poses a risk of gastrointestinal infection. Although mother's milk may be a potential vehicle, no evidence exists to indicate that antibiotics dissolved in human milk are bioequivalent to those dissolved in water. Therefore, we compared pharmacokinetic parameters of an orally administered antibiotic, amoxicillin, dissolved in human milk, to those of water-dissolved amoxicillin.MethodsA pharmacokinetic study was conducted in 16 healthy adult volunteers in a randomised crossover design. Marketed amoxicillin powder for suspension was dissolved in either human milk or water at a final concentration of 50 mg/mL, and 10 mL was given orally in a fasting state. Timed blood samples were obtained and plasma amoxicillin was quantified using liquid chromatography-mass spectrometry.FindingsResults showed that pharmacokinetic parameters, including area-under-the-curve, Cmax and half-life of the water-based and milk-based amoxicillin administration were not significantly different. 90% CIs of the ratios of these parameters in concomitant breast milk administration to those of water were within 89% and 116%, suggesting they are bioequivalent (defined as a range between 80% and 125%).InterpretationWe conclude that oral administration of amoxicillin dissolved in human milk at 50 mg/mL results in pharmacokinetics profiles comparable to amoxicillin dissolved in water. Pharmaceutical interactions between amoxicillin and breast milk are unlikely, suggesting no need to modify dosing schedules.

Pharmacokinetic comparison of two buprenorphine formulations after buccal administration in healthy male cats

2017 ◽  
Vol 20 (4) ◽  
pp. 312-318 ◽  
Author(s):  
Brett M Gulledge ◽  
Kristen M Messenger ◽  
Karen K Cornell ◽  
Heather Lindell ◽  
Chad W Schmiedt
Keyword(s):  
Liquid Chromatography ◽  
Maximum Concentration ◽  
High Performance ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Storage Condition ◽  
Healthy Male ◽  
Limit Of Quantification ◽  
Significant Difference ◽  
Extent Of Absorption

Objectives The objective of this study was to compare the pharmacokinetics of compounded and commercially available aqueous formulations of buprenorphine after a single buccal dose to healthy cats and to evaluate the concentrations of a compounded buprenorphine solution over 21 days when stored at room temperature (RT; 22–24°C) with exposure to light or when refrigerated at 4°C while protected from light. Methods Six young healthy male cats were administered single buccal doses of compounded and commercially available formulations of buprenorphine (0.03 mg/kg) using a randomized, blinded, two-period crossover design. Blood samples were obtained over a 24 h period and plasma buprenorphine concentrations were determined using ultra-high-pressure liquid chromatography with mass spectrometry detection. Three batches of the compounded formulation were stored at RT or 4°C and aliquots were evaluated over 21 days for buprenorphine concentration using high-performance liquid chromatography with fluorescence detection. Results Plasma concentrations of buprenorphine were above the limit of quantification up to 6 h in some cats and up to 3 h in all cats. The area under the curve was significantly less for the compounded formulation ( P = 0.004). A significant difference was not detected between formulations for time to maximum concentration ( P = 0.11), maximum concentration ( P = 0.06), half-life ( P = 0.88) and mean residence time ( P = 0.57). Buprenorphine concentration in the compounded formulation was not affected by storage condition or time and remained between 90% and 110% of the target concentration at all time points. Conclusions and relevance A buprenorphine solution prepared from sublingual tablets is absorbed after buccal administration in healthy cats. The extent of absorption is significantly less than that of the commercially available formulation. The compounded solution maintains an acceptable buprenorphine concentration for at least 21 days when stored at RT or refrigerated.

scholarly journals The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice

2009 ◽  
Vol 102 (2) ◽  
pp. 242-248 ◽  
Author(s):  
Takashi Hashimoto ◽  
Yoshiaki Ozaki ◽  
Mayuko Taminato ◽  
Swadesh K. Das ◽  
Masashi Mizuno ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oral Administration ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Low Concentration ◽  
Single Oral Administration ◽  
Daily Oral Administration

The pharmacokinetics of dietary fucoxanthin, one of the xanthophylls in brown sea algae, is little understood. In the present study, mice were orally administered fucoxanthin, and the distribution and accumulation of fucoxanthin and its metabolites fucoxanthinol and amarouciaxanthin A were measured in the plasma, erythrocytes, liver, lung, kidney, heart, spleen and adipose tissue. In a single oral administration of 160 nmol fucoxanthin, fucoxanthinol and amarouciaxanthin A were detectable in all specimens tested in the present study, but fucoxanthin was not. The time at maximum concentration (Tmax) of these metabolites in adipose tissue was 24 h, while the Tmax in the others was 4 h. The area under the curve to infinity (AUC∞) of fucoxanthinol in the liver was the highest value (4680 nmol/g × h) among the tissues tested in the present study, while the AUC∞ of amarouciaxanthin A in adipose tissue was the highest value (4630 nmol/g × h). In daily oral administration of 160 nmol fucoxanthin for 1 week, fucoxanthin was also detectable in the tissues even at a low concentration. The amount of fucoxanthinol was 123 nmol/g in the heart and 85·2 nmol/g in the liver. Amarouciaxanthin A in the adipose tissue was distributed at a concentration of 97·5 nmol/g. These results demonstrate that dietary fucoxanthin accumulates in the heart and liver as fucoxanthinol and in adipose tissue as amarouciaxanthin A.

Blood-to-saliva glucose time lag in sedated healthy dogs

2021 ◽  
pp. 104063872110353
Author(s):  
Antonia Ioannou ◽  
Heidi Phillips ◽  
Stephanie Keating ◽  
Anne Barger ◽  
Nicolas Lopez-Villalobos ◽  
...  
Keyword(s):  
Glucose Concentration ◽  
Repeated Measures ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Time Lag ◽  
Area Under The Curve ◽  
Oral Bacteria ◽  
Glucose Levels ◽  
Healthy Dogs ◽  
Paired Serum

The management of diabetes mellitus mandates measurement of blood glucose. Saliva offers an alternative to blood sampling, but measurement of the salivary glucose concentration is difficult, and the blood-to-saliva glucose time lag is uncertain. We aimed to determine the serum–saliva glucose time lag in the saliva of healthy dogs. The combined duct of the mandibular and sublingual salivary glands of 6 dogs was cannulated to collect saliva and prevent glucose degradation by oral bacteria. Following a 0.25 g/kg IV bolus of dextrose, paired serum–saliva samples were collected at baseline and in twelve 5-min blocks over 60 min. Serum and salivary glucose levels were analyzed with a linear mixed model for repeated measures with a compound symmetry error structure. Mean (±SD) saliva production was 10.3 ± 2.9 µL/kg/min, and the area under the curve (AUCglucose)saliva/serum ratio was 0.006, which highlights the magnitude of the large difference in glucose concentration between the 2 compartments. The serum–saliva glucose time lag was 30–40 min.

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