scholarly journals Pharmacokinetic Properties of Adenosine Amine Congener in Cochlear Perilymph after Systemic Administration

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Hao Chang ◽  
Ravindra S. Telang ◽  
Sreevalsan Sreebhavan ◽  
Malcolm Tingle ◽  
Peter R. Thorne ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Intravenous Administration ◽  
Mass Spectrometry Detection ◽  
Cochlear Blood Flow ◽  
Adenosine Receptor Agonist ◽  
Pharmacokinetic Properties ◽  
Liquid Chromatography Tandem Mass ◽  
The Usa ◽  
Minimal Effective Concentration ◽  
Global Health Problem

Noise-induced hearing loss (NIHL) is a global health problem affecting over 5% of the population worldwide. We have shown previously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors in the inner ear, and a selective A1adenosine receptor agonist adenosine amine congener (ADAC) has emerged as a potentially effective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties of ADAC in rat perilymph after systemic (intravenous) administration using a newly developed liquid chromatography-tandem mass spectrometry detection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy, precision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with the cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and remained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC was significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or cochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural hearing loss caused by exposure to traumatic noise.

Application of an LC-MS/MS Method to a Urinary Excretion Study of Triflusal and its Main Metabolite 2-hydroxy-4-trifluoromethyl Benzoic Acid in Human Urine

2020 ◽  
Vol 16 (3) ◽  
pp. 328-334
Author(s):  
Jie Ge ◽  
Jin-Wen Wang ◽  
Qi-Yan Guo ◽  
Ai-Dong Wen
Keyword(s):  
Benzoic Acid ◽  
Urinary Excretion ◽  
Human Urine ◽  
Multiple Reaction Monitoring ◽  
Main Metabolite ◽  
Linear Relationships ◽  
Pharmacokinetic Properties ◽  
Liquid Chromatography Tandem Mass ◽  
Excretion Study ◽  
Acetate Aqueous Solution

Objective: A validated liquid chromatography-tandem mass spectrometry method (LCMS/ MS) was established to simultaneously determine the concentration of triflusal and its main metabolite 2-hydroxy-4-trifluoromethyl benzoic acid(HTB) in human urine. Methods: The separation was performed on a Dikma C18 column using isocratic elution with acetonitrile-4 mmol/L ammonium acetate aqueous solution containing 0.3 % formic acid water (78: 28, V/V). The method involved extraction with methanol using protein precipitation. The precursor-toproduct ion transitions with multiple reaction monitoring was m/z 247.1→161.1, 204.8→106.7and 136.9→93.0 for triflusal, HTB and salicylic acid(IS), respectively. The method showed good linear relationships over the ranges of 0.08 to 48 μg/mL and0.5 to 50 μg/mL. Results: It was the first time that a urinary excretion study of triflusal capsule as oral. The cumulative urinary recovery showed 8.5% and 2.7% for triflusal and HTB, respectively. Conclusion: This method was successfully used for evaluating the pharmacokinetic properties of triflusal and HTB in urine in Chinese healthy subjects.

Abstract P476: 8-Aminoguanosine Exerts Diuretic and Natriuretic Activity via Conversion to 8-Aminoguanine

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Edwin K Jackson ◽  
Zaichuan Mi
Keyword(s):  
Intravenous Administration ◽  
Sodium Excretion ◽  
Antihypertensive Drugs ◽  
Urine Volume ◽  
Systemic Circulation ◽  
Tandem Mass ◽  
Contralateral Kidney ◽  
New Class ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

We previously reported that 8-aminoguanosine and 8-aminoguanine are potent and efficacious K + -sparing diuretics/natriuretics that may represent a new class of antihypertensive drugs. Moreover, because these compounds are endogenous, they may have physiological roles. It is possible that the diuretic/natriuretic activity of 8-aminoguanosine is mediated mostly via conversion to 8-aminoguanine. To test this concept, we conducted 3 protocols in anesthetized rats. The 1 st protocol demonstrated that at 85 to 115 min post intravenous administration, both 8-aminoguanosine and 8-aminoguanine (33.5 μmol/kg) significantly increased urine volume [ml/min: 8-aminoguanosine from 0.3 ± 0.1 to 0.9 ± 0.1 (mean ± SEM; n=7); 8-aminoguanine from 0.3 ± 0.1 to 1.5 ± 0.2 (n=8)] and sodium excretion (μmol/min: 8-aminoguanosine from 12 ± 6 to 109 ± 21; 8-aminoguanine from 18 ± 8 to 216 ± 31). The 2 nd protocol showed that intrarenal artery infusions of 8-aminoguanosine (from 0.1 to 1 μmol/kg/min) did not affect urine volume or sodium excretion in either the ipsilateral or contralateral kidney. In contrast, intrarenal artery infusions of 8-aminoguanine significantly increased ipsilateral (but not contralateral) urine volume [at 1 μmol/kg/min from 0.2 ± 0.02 to 0.7 ± 0.1 (n=17)] and sodium excretion (from 24 ± 4 to 216 ± 31). In a 3 rd protocol we administered 8-aminoguanosine and 8-aminoguanine intravenously (33.5 μmol/kg) and measured renal interstitial (medulla) levels of 8-aminoguanosine and 8-aminoguanine using microdialysis combined with ultraperformance liquid chromatography-tandem mass spectrometry. Intravenous administration of 8-aminoguanosine and 8-aminoguanine similarly increased renal interstitial levels of 8-aminoguanine [ng/ml; 8-aminoguanosine from 4 ± 1 to 1025 ± 393 (n=6), and 8-aminoguanine from 2 ± 1 to 1069 ± 407 (n=6)]. Neither 8-aminoguanosine nor 8-aminoguanine affected renal interstitial levels of 8-aminoguanosine. Together these data clearly show that the renal effects of 8-aminoguanosine are not direct, but require conversion in the systemic circulation to 8-aminoguanine. If 8-aminoguanosine is physiologically important it should be viewed as a “pro-hormone.” As a pharmacological agent, it is best described as a “pro-drug.”

scholarly journals Preclinical Pharmacokinetics of Scoparone, Geniposide and Rhein in an Herbal Medicine Using a Validated LC-MS/MS Method

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2716 ◽  
Author(s):  
Tun-Pin Hsueh ◽  
Tung-Hu Tsai
Keyword(s):  
Bioactive Compounds ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Low Dose ◽  
Rat Plasma ◽  
Herbal Formula ◽  
Preclinical Pharmacokinetics ◽  
Pharmacokinetic Properties ◽  
Liquid Chromatography Tandem Mass

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of scoparone, geniposide and rhein in rat plasma. A pharmaceutical herbal powder was administered to rats at doses of 1 g/kg and 3 g/kg orally. The method showed excellent linearity (r2 > 0.999) and validation was successfully conducted for the pharmacokinetic study. The results show that the Cmax values and areas under the curve of scoparone, geniposide and rhein were higher and not proportional to the dose in rat plasma, while the Tmax and half-life values were consistent in the group that received 1 g/kg. The clearance of the higher dose (3 g/kg) did not decrease proportionally to that of the low dose. The results showed the nonlinear pharmacokinetic properties of scoparone, geniposide and rhein in Yin-Chen-Hao-Tang that suggested possible accumulation of bioactive compounds through oral administration. This pharmacokinetic study reveals that an increased dose of this herbal formula would largely increase the maximum concentration and bioavailability of scoparone, geniposide and rhein.

scholarly journals Physicochemical Effects of the Major Quassinoids in a Standardized Eurycoma longifolia Extract (Fr 2) on the Bioavailability and Pharmacokinetic Properties, and their Implications for Oral Antimalarial Activity

2011 ◽  
Vol 6 (3) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Bin-Seng Low ◽  
Chin-Hoe Teh ◽  
Kah-Hay Yuen ◽  
Kit-Lam Chan
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Antimalarial Activity ◽  
Elimination Rate ◽  
Rat Plasma ◽  
Chemical Degradation ◽  
Absolute Bioavailability ◽  
Phytochemical Analysis ◽  
Eurycoma Longifolia ◽  
Pharmacokinetic Properties

A simple validated LC-UV method for the phytochemical analysis of four bioactive quassinoids, 13α(21)-epoxyeurycomanone (EP), eurycomanone (EN), 13α,21-dihydroeurycomanone (ED) and eurycomanol (EL) in rat plasma following oral (200 mg/kg) and intravenous administration (10 mg/kg) of a standardized extract Fr 2 of Eurycoma longifolia Jack was developed for pharmacokinetic and bioavailability studies. The extract Fr 2 contained 4.0%, 18.5%, 0.7% and 9.5% of EP, EN, ED and EL, respectively. Following intravenous administration, EP displayed a relatively longer biological half-life (t½ = 0.75 ± 0.25 h) due primarily to its lower elimination rate constant (ke) of 0.84 ± 0.26 h−1) when compared with the t½ of 0.35 ± 0.04 h and ke of 2.14 ± 0.27 h−1, respectively of EN. Following oral administration, EP showed a higher Cmax of 1.61± 0.41 μg/mL over that of EN (Cmax = 0.53 ± 0.10 μg/mL). The absolute bioavailability of EP was 9.5-fold higher than that of EN, not because of chemical degradation since both quassinoids were stable at the simulated gastric pH of 1. Instead, the higher log Kow value of EP (-0.43) contributed to greater membrane permeability over that of EN (log Kow = −1.46) at pH 1. In contrast, EL, being in higher concentration in the extract than EP, was not detected in the plasma after oral administration because of substantial degradation by the gastric juices after 2 h. Similarly, ED, being unstable at the acidic pH and together with its low concentration in Fr 2, was not detectable in the rat plasma. In conclusion, upon oral administration of the bioactive standardized extract Fr 2, EP and EN may be the only quassinoids contributing to the overall antimalarial activity; this is worthy of further investigation.

scholarly journals Pharmacokinetics of Amodiaquine and Desethylamodiaquine in Pregnant and Postpartum Women with Plasmodium vivax Malaria

2011 ◽  
Vol 55 (9) ◽  
pp. 4338-4342 ◽  
Author(s):  
Marcus J. Rijken ◽  
Rose McGready ◽  
Vincent Jullien ◽  
Joel Tarning ◽  
Niklas Lindegardh ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Dosing Regimen ◽  
Noncompartmental Analysis ◽  
Time Data ◽  
Content Type ◽  
Concentration Time ◽  
Chromatography Tandem Mass Spectrometry ◽  
Pharmacokinetic Properties ◽  
Plasmodium Vivax Malaria ◽  
Liquid Chromatography Tandem Mass

ABSTRACTIn order to study the pharmacokinetic properties of amodiaquine and desethylamodiaquine during pregnancy, 24 pregnant women in the second and third trimesters of pregnancy and withPlasmodium vivaxmalaria were treated with amodiaquine (10 mg/kg of body weight/day) for 3 days. The same women were studied again at 3 months postpartum. Plasma was analyzed for amodiaquine and desethylamodiaquine by use of a liquid chromatography-tandem mass spectrometry method. Individual concentration-time data were evaluated using noncompartmental analysis. There were no clinically relevant differences in the pharmacokinetics of amodiaquine and desethylamodiaquine between pregnant (n= 24) and postpartum (n= 18) women. The results suggest that the current amodiaquine dosing regimen is adequate for the treatment ofP. vivaxinfections during pregnancy.

scholarly journals Diet quality and hearing loss among middle–older aged adults in the USA: findings from National Health and Nutrition Examination Survey

2019 ◽  
Vol 23 (5) ◽  
pp. 812-820 ◽  
Author(s):  
Qiushi Huang ◽  
Yichen Jin ◽  
Nicholas S Reed ◽  
Yan Ma ◽  
Melinda C Power ◽  
...  
Keyword(s):  
Hearing Loss ◽  
National Health ◽  
Diet Quality ◽  
Longitudinal Design ◽  
Low Frequency ◽  
Inverse Association ◽  
Cross Sectional ◽  
Health And Nutrition ◽  
Hearing Function ◽  
The Usa

AbstractObjective:To examine the associations between overall diet quality and hearing function among middle–older aged adults in the USA.Design:Cross-sectional analysis. Diet quality was examined using the Mediterranean Diet Score (MDS), using data from a single 24 h dietary recall. Hearing function was objectively measured by audiometry assessments and hearing loss, including high- and low-frequency hearing loss, was defined as pure-tone averages at specific ranges of hearing frequencies >25 dB. Weighted logistic regression analyses were performed to examine the associations of MDS (scored 0–9, categorized at the median as ≤3 or >3) with hearing loss and high- and low-frequency hearing loss.Setting:National Health and Nutrition Examination Surveys 2000–2006 and 2009–2012.Participants:Adults aged ≥50 years (n 1639) with valid dietary and audiometry assessments.Results:After adjusting for potential confounders, a non-significant trend for a protective association of higher MDS was observed for hearing loss (OR = 0·78; 95 % CI 0·49, 1·23). A significant inverse association was observed for high-frequency hearing loss (OR = 0·64; 95 % CI 0·43, 0·95). No association was found for low-frequency hearing loss among women; however, higher MDS was significantly associated with higher odds of low-frequency hearing loss among men (OR = 2·63; 95 % CI 1·39, 4·95).Conclusions:Among middle–older aged adults, adherence to a Mediterranean-style diet was inversely associated with hearing loss, including those at high hearing frequencies, among older adults. However, a detrimental association was observed at low hearing frequencies among men. Future investigations with a longitudinal design are needed to clarify the associations between diet quality and hearing loss.

Continuous Infusion of Naloxone in the Treatment of Narcotic Overdose

1981 ◽  
Vol 15 (12) ◽  
pp. 945-950 ◽  
Author(s):  
J. Chris Bradberry ◽  
Marsha A. Raebel
Keyword(s):  
Continuous Infusion ◽  
Intravenous Administration ◽  
Clinical Studies ◽  
Case Reports ◽  
Mode Of Administration ◽  
Pharmacokinetic Properties ◽  
Infusion Method

This paper describes case reports and pharmacokinetic information regarding the continuous intravenous administration of naloxone in treatment of narcotic overdose. Continuous naloxone infusion has been used successfully in acutely narcotized patients, and a review of the pharmacodynamic and pharmacokinetic properties of naloxone indicate the reasons for this mode of administration. Summaries of clinical studies in support of the infusion method are given. A naloxone protocol is outlined.

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