scholarly journals The pharmacokinetic interaction between nasally administered naloxone and the opioid remifentanil in human volunteers

2021 ◽  
Author(s):  
Ida Tylleskar ◽  
Sissel Skarra ◽  
Arne Kristian Skulberg ◽  
Ola Dale
Keyword(s):  
Maximum Concentration ◽  
Intranasal Administration ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Intramuscular Administration ◽  
Nasal Administration ◽  
Pharmacokinetic Studies ◽  
Remifentanil Infusion ◽  
Human Volunteers ◽  
Significant Difference

Abstract Purpose Remifentanil has been shown to increase the bioavailability of nasally administered naloxone. The aim of this study was to explore the nature of this observation. Methods We analysed samples from three pharmacokinetic studies to determine the serum concentrations of naloxone-3-glucuronide (N3G), the main metabolite of naloxone, with or without exposure to remifentanil. To enable direct comparison of the three studies, the data are presented as metabolic ratios (ratio of metabolite to mother substance, N3G/naloxone) and dose-corrected values of the area under the curve and maximum concentration (Cmax). Results Under remifentanil exposure, the time to maximum concentration (Tmax) for N3G was significantly higher for intranasal administration of 71 min compared to intramuscular administration of 40 min. The dose-corrected Cmax of N3G after intranasal administration of naloxone under remifentanil exposure was significantly lower (4.5 ng/mL) than in subjects not exposed to remifentanil (7.8–8.4 ng/mL). The metabolic ratios after intranasal administration rose quickly after 30–90 min and were 2–3 times higher at 360 min compared to intravenous and intramuscular administration. Remifentanil exposure resulted in a much slower increase of the N3G/naloxone ratio after intranasal administration compared to intranasal administration with the absence of remifentanil. After remifentanil infusion was discontinued, this effect gradually diminished. From 240 min there was no significant difference between the ratios observed after intranasal naloxone administration. Conclusion Remifentanil increases the bioavailability of naloxone after nasal administration by reducing the pre-systemic metabolism of the swallowed part of the nasal dose.

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 Preclinical Monitoring of Drug Association in Experimental Chemotherapy of Chagas' Disease by a New HPLC-UV Method

2012 ◽  
Vol 56 (6) ◽  
pp. 3344-3348 ◽  
Author(s):  
Rodrigo Moreira da Silva ◽  
Líliam Teixeira Oliveira ◽  
Neila Márcia Silva Barcellos ◽  
Jacqueline de Souza ◽  
Marta de Lana
Keyword(s):  
Chagas Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Volume Of Distribution ◽  
Experimental Chemotherapy ◽  
Content Type ◽  
Therapeutic Regime ◽  
Significant Difference

ABSTRACTA combination of drugs in experimental chemotherapy of Chagas' disease may increase the effectiveness of treatment. To evaluate the possible mechanisms that influence the improvement of therapy, we investigated the pharmacokinetic interaction between benznidazole and itraconazole in a murine model treated orally with single doses of 5 mg of each compound separately or together. Blood samples from treated mice were collected at different intervals for 48 h, and a high-performance liquid chromatography (HPLC)-UV method was used to quantify both drugs in the plasma. A decrease of 1.5-fold in the maximum drug concentration in the plasma (Cmax) and an increase of 2.66-fold in the volume of distribution (V) and 7.5-fold in the elimination half-life (t1/2β) of benznidazole when coadministered with itraconazole were observed. The parameters area under the curve (AUC0-t), area under the curve extrapolated to infinity (AUC0-∞), time to maximum concentration of drug in serum (Tmax), and clearance (CL) for benznidazole were not significantly different in this therapeutic regime. None of the evaluated parameters for ITC demonstrated a significant difference between isolated and associated administration. These results suggest that the main effect of this interaction leads to accumulation of benznidazole in the biological system. This effect may contribute to the improved therapeutic efficacy of this combination of drugs, in addition to synergism of the different mechanisms of action of benznidazole and itraconazole againstTrypanosoma cruzi in vivo.

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.

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.

Glucuronidation and its effect on the bioactivity of amentoflavone, a biflavonoid from Ginkgo biloba leaves

2020 ◽  
Author(s):  
Lili Gan ◽  
Jiating Ma ◽  
Guoquan You ◽  
Jinxia Mai ◽  
Zhaoyu Wang ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Anticancer Activity ◽  
Ginkgo Biloba ◽  
Metabolic Profile ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Pharmacokinetic Studies ◽  
Significant Difference ◽  
Dietary Flavonoid ◽  
U251 Cells

Abstract Objectives Ginkgo biloba leaves contain amentoflavone (AMF), a dietary flavonoid that possesses antioxidant and anticancer activity. Flavonoids are extensively subjected to glucuronidation. This study aimed to determine the metabolic profile of AMF and the effect of glucuronidation on AMF bioactivity. Methods A pharmacokinetic study was conducted to determine the plasma concentrations of AMF and its metabolites. The metabolic profile of AMF was elucidated using different species of microsomes. The antioxidant activity of AMF metabolites was determined using DPPH/ABTS radical and nitric oxide assays. The anticancer activity of AMF metabolites was evaluated in U87MG/U251 cells. Key findings Pharmacokinetic studies indicated that the oral bioavailability of AMF was 0.06 ± 0.04%, and the area under the curve of the glucuronidated AMF metabolites (410.938 ± 62.219 ng/ml h) was significantly higher than that of AMF (194.509 ± 16.915 ng/ml h). UGT1A1 and UGT1A3 greatly metabolized AMF. No significant difference was observed in the antioxidant activity between AMF and its metabolites. The anticancer activity of AMF metabolites significantly decreased. Conclusions A low AMF bioavailability was due to extensive glucuronidation, which was mediated by UGT1A1 and UGT1A3. Glucuronidated AMF metabolites had the same antioxidant but had a lower anticancer activity than that of AMF.

scholarly journals Pharmacokinetics of Mephedrone Enantiomers in Whole Blood after a Controlled Intranasal Administration to Healthy Human Volunteers

2020 ◽  
Vol 14 (1) ◽  
pp. 5
Author(s):  
Joanna Czerwinska ◽  
Mark C. Parkin ◽  
Agostino Cilibrizzi ◽  
Claire George ◽  
Andrew T. Kicman ◽  
...  
Keyword(s):  
Whole Blood ◽  
Intranasal Administration ◽  
Chiral Recognition ◽  
Area Under The Curve ◽  
Healthy Human ◽  
Enantiomeric Ratio ◽  
Human Volunteers ◽  
Liquid Chromatography Tandem Mass ◽  
Neurological Effects ◽  
Enantioselective Pharmacokinetics

Mephedrone, which is one of the most popular synthetic cathinones, has one chiral centre and thus exists as two enantiomers: R-(+)-mephedrone and S-(−)-mephedrone. There are some preliminary data suggesting that the enantiomers of mephedrone may display enantioselective pharmacokinetics and exhibit different neurological effects. In this study, enantiomers of mephedrone were resolved via chromatographic chiral recognition and the absolute configuration was unambiguously determined by a combination of elution order and chiroptical analysis (i.e., circular dichroism). A chiral liquid chromatography tandem mass spectrometry method was fully validated and was applied to the analysis of whole blood samples collected from a controlled intranasal administration of racemic mephedrone hydrochloride to healthy male volunteers. Both enantiomers showed similar kinetics, however, R-(+)-mephedrone had a greater mean Cmax of 48.5 ± 11.9 ng/mL and a longer mean half-life of 1.92 ± 0.27 h compared with 44.6 ± 11.8 ng/mL and 1.63 ± 0.23 h for S-(−)-mephedrone, respectively. Moreover, R-(+)-mephedrone had a lower mean clearance and roughly 1.3 times greater mean area under the curve than S-(−)-mephedrone. Significant changes in the enantiomeric ratio over time were observed, which suggest that the analytes exhibit enantioselective pharmacokinetics. Even though the clinical significance of this finding is not yet fully understood, the study confirms that the chiral nature, and consequently the enantiomeric purity of mephedrone, can be a crucial consideration when interpreting toxicological results.

scholarly journals Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract

2011 ◽  
Vol 107 (11) ◽  
pp. 1566-1569 ◽  
Author(s):  
Takashi Hashimoto ◽  
Yoshiaki Ozaki ◽  
Masashi Mizuno ◽  
Masaru Yoshida ◽  
Yosuke Nishitani ◽  
...  
Keyword(s):  
Oral Administration ◽  
Human Plasma ◽  
Peripheral Blood ◽  
Maximum Concentration ◽  
Active Metabolite ◽  
Human Subjects ◽  
Area Under The Curve ◽  
The Other ◽  
Half Time ◽  
Human Volunteers

Dietary fucoxanthin has been reported to exert several physiological functions, and fucoxanthinol is considered to be the primary active metabolite of fucoxanthin. However, there is no information about the pharmacokinetics of fucoxanthinol in human subjects. In the present study, eighteen human volunteers were orally administered kombu extract containing 31 mg fucoxanthin, and their peripheral blood was collected 5 min before and 0·5, 1, 2, 4, 8 and 24 h after the treatment. Plasma fucoxanthinol concentrations were measured by HPLC, and the pharmacokinetics of fucoxanthinol were as follows: maximum concentration, 44·2 nmol/l; time at maximum concentration, 4 h; terminal half-time, 7·0 h; area under the curve (AUC) for 1–24 h, 578·7 nmol/l × h; AUC(∞), 663·7 nmol/l × h. In addition to fucoxanthinol, we also attempted to detect amarouciaxanthin A, a hepatic metabolite of fucoxanthinol, using HPLC, but it was not present in the volunteers' plasma. On the other hand, a peak that was suspected to represent the cis-isomer of fucoxanthinol was found in the HPLC chromatogram. By comparing the present results with those of a previous study using mice, we found that the bioavailability and metabolism of fucoxanthinol differ between human subjects and mice.

GROWTH HORMONE RESPONSES TO FRUCTOSE IN DIABETES MELLITUS

1974 ◽  
Vol 75 (3) ◽  
pp. 497-502
Author(s):  
Mayer B. Davidson ◽  
Roger M. Steele
Keyword(s):  
Diabetes Mellitus ◽  
Growth Hormone ◽  
Fasting Glucose ◽  
Area Under The Curve ◽  
Oral Glucose ◽  
Gh Secretion ◽  
Significant Difference ◽  
Duration Of Disease ◽  
Hormone Responses

ABSTRACT Since fructose is normally metabolized in diabetics and has recently been shown to stimulate GH secretion, it was used to assess GH responses in diabetics. Fourteen diabetics (9 on insulin) and 8 controls matched for weight were studied. Fructose, infused over 10 min, was compared to arginine, infused over 30 min, both at 0.5 g/kg. Samples were collected at 0, 30, 60, 90 and 120 min and GH responses assessed as area under the curve minus the fasting area. There was no significant difference between the GH responses in diabetics and controls to either agent. Responses to arginine and fructose were significantly correlated (r = 0.60, P < 0.01) in all subjects, but not related to therapy, duration of disease or fasting glucose (75–287 mg/100 ml) in the diabetics. Oral glucose blunted the GH response to fructose in 2 controls. It is concluded that 1) fructose can stimulate GH secretion in male diabetics; 2) however, fructose-stimulated GH responses are not increased in diabetes mellitus.

Physical Activity Level and Motor Aptitude: Motor Domains and Identification Capacity of Brazilian Insufficiently Active Older Adults

2020 ◽  
Vol 13 ◽  
Author(s):  
Lucia Maria Andreis ◽  
Fernando de Aguiar Lemos ◽  
Lorenna Walesca de Lima Silva ◽  
Cassiana Luiza Pistorello Garcia ◽  
Gabrielli Veras ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Physical Activity Level ◽  
Area Under The Curve ◽  
The Elderly ◽  
Activity Level ◽  
General Motor ◽  
Body Scheme ◽  
Significant Difference ◽  
Global Coordination

Background: A decrease in the physical activity level in old age is common, which results in an increase in the number of falls and chronic conditions. Associated with that occurs the decline in motor skills as a result of the deficit in the interaction of cognitive and motor processes. Physical activity level can be associated differently with each motor domains. Objective: We analyzed the relationship between physical activity level and motor aptitude, and to identify which motor domains were most sensitive to detect insufficiently active level in older adults. Methods: Participated in the study 385 elderly people of both sexes. For the evaluation of the subjects were adopted the International Questionnaire on Physical Activity and the Motor Scale for Older Adults. Results: The majority of the elderly were active. In the comparison of motor aptitude between active and insufficiently active (IAC) elders a significant difference was found in the Global Coordination, Balance, Body Scheme and General Motor Aptitude. From the analysis of the area under the curve (AUC), we verified that these domains also were the ones that presented adequate diagnostic accuracy to identify IAC elderly. Besides that active elderly have presented the General Motor Aptitude classified within normality while the IAC below the normal. Conclusion: Our data suggest that IAC older adults present lower motor aptitude than the active elderly, especially in the domains of Global Coordination, Balance, Body Scheme and General Motor Aptitude, and that these domains were sensitive to indicate IAC older adults.

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