Oral Transmucosal Etomidate in Volunteers 

1998 ◽  
Vol 88 (1) ◽  
pp. 89-95 ◽  
Author(s):  
James B. Streisand ◽  
Ruurd L. Jaarsma ◽  
Mason A. Gay ◽  
Mary Jane Badger ◽  
Lynn Maland ◽  
...  
Keyword(s):  
Side Effects ◽  
Dosage Form ◽  
Time Course ◽  
Venous Blood ◽  
Pharmacokinetic Profile ◽  
Clinically Significant ◽  
Transmucosal Administration ◽  
Further Development ◽  
Adult Volunteers ◽  
Transmucosal Delivery

Background The oral transmucosal route of delivery is now used for many drugs, including fentanyl and midazolam. Etomidate's pharmacokinetic profile and physiochemical properties suggest it may be suitable for transmucosal delivery. Transmucosal delivery might extend etomidate's use to sedation and anxiolysis. This is the first study in humans to examine the oral transmucosal administration of a novel etomidate dosage form. Methods Ten healthy adult volunteers consumed 12.5-mg, 25-mg, 50-mg, and 100-mg doses of oral transmucosal etomidate (OTET) on four different study days. Serum etomidate concentrations, sedation, respiratory and cardiovascular variables, taste, and side effects were determined. Results Five minutes after OTET administration, etomidate was detected in the venous blood. Mean peak concentrations occurred 20-30 min later and ranged from 61-174 ng/ml, related to the dose administered. Drowsiness and light sleep occurred in a dose-related manner 10-20 min after administration and lasted for 30-60 min. No episodes of SpO2 <90%, hypotension, or emesis occurred at any dose throughout the study. Nausea was rare. Two volunteers exhibited a brief episode of involuntary tremor after the 100-mg dose. The bitter taste of OTET was judged increasingly unpleasant with escalating doses. Conclusions Oral transmucosal etomidate produces dose-related increases in sedation and clinically significant serum concentrations with minimal side effects. The time course of these effects suggests that OTET might be useful when brief mild to moderate sedation with rapid recovery is desirable. Further development of this novel dosage form is warranted.

Significance of In-Vitro and In-Vivo Correlation in Drug Delivery System

2018 ◽  
Vol 4 (4) ◽  
pp. 523-531
Author(s):  
Hina Mumtaz ◽  
Muhammad Asim Farooq ◽  
Zainab Batool ◽  
Anam Ahsan ◽  
Ashikujaman Syed
Keyword(s):  
Dosage Form ◽  
Pharmaceutical Preparations ◽  
Pharmacokinetic Profile ◽  
In Vitro Dissolution ◽  
Time Saving ◽  
Pharmaceutical Dosage Form ◽  
Short Period ◽  
Form Development

The main purpose of development pharmaceutical dosage form is to find out the in vivo and in vitro behavior of dosage form. This challenge is overcome by implementation of in-vivo and in-vitro correlation. Application of this technique is economical and time saving in dosage form development. It shortens the period of development dosage form as well as improves product quality. IVIVC reduce the experimental study on human because IVIVC involves the in vivo relevant media utilization in vitro specifications. The key goal of IVIVC is to serve as alternate for in vivo bioavailability studies and serve as justification for bio waivers. IVIVC follows the specifications and relevant quality control parameters that lead to improvement in pharmaceutical dosage form development in short period of time. Recently in-vivo in-vitro correlation (IVIVC) has found application to predict the pharmacokinetic behaviour of pharmaceutical preparations. It has emerged as a reliable tool to find the mode of absorption of several dosage forms. It is used to correlate the in-vitro dissolution with in vivo pharmacokinetic profile. IVIVC made use to predict the bioavailability of the drug of particular dosage form. IVIVC is satisfactory for the therapeutic release profile specifications of the formulation. IVIVC model has capability to predict plasma drug concentration from in vitro dissolution media.

scholarly journals Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 508
Author(s):  
Sara Silva ◽  
António J. Almeida ◽  
Nuno Vale
Keyword(s):  
Side Effects ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Pharmacokinetic Profile ◽  
The Elderly ◽  
Motor Symptoms ◽  
Administration Routes ◽  
Pharmaceutical Therapy ◽  
Drug Pharmacokinetic ◽  
The Brain

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

National Cancer Institute–United States strategy regarding intraperitoneal chemotherapy for ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 26-28 ◽  
Author(s):  
E. L. Trimble ◽  
M. C. Christian
Keyword(s):  
Ovarian Cancer ◽  
National Cancer Institute ◽  
Phase Iii ◽  
Cooperative Groups ◽  
Advocacy Organizations ◽  
Increased Risk ◽  
Phase Iii Trials ◽  
Educational Campaign ◽  
Clinically Significant ◽  
Further Development

On the basis of three large randomized phase III trials, the National Cancer Institute (NCI) issued a Clinical Announcement in January 2006 recommending that women with optimally debulked stage III ovarian cancer and their physicians consider a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy. The combination of IV and IP chemotherapy is associated with a clinically significant benefit in survival, although it does also confer an increased risk of toxicity compared to IV chemotherapy alone. The NCI Clinical Announcement was issued as part of a broader educational campaign, designed in conjunction with professional societies, cancer centers, Clinical Trials Cooperative Groups, and cancer advocacy organizations. The further development of IP chemotherapy in ovarian cancer requires additional clinical and translational research

scholarly journals The speed of reinfusion affects the vascular system during ozone major autohemotherapy

Ozone Therapy ◽  
2017 ◽  
Vol 1 (3) ◽  
pp. 56 ◽  
Author(s):  
Daniele Rimini ◽  
Filippo Molinari ◽  
William Liboni ◽  
Vincenzo Simonetti ◽  
Marianno Franzini
Keyword(s):  
Infrared Spectroscopy ◽  
Side Effects ◽  
Near Infrared Spectroscopy ◽  
Transcranial Doppler ◽  
Near Infrared ◽  
Vascular System ◽  
Venous Blood ◽  
Blood Drawing

Ozone major autohemotherapy (O-MAHT) is a way of ozonetherapy administration consisting of drawing patient’s venous blood, mixing with oxygen/ozone, and reinfusing it into the vein. Some ozone therapists reported side effects during the O-MAHT, but the origin has not been described yet. We investigated the effect of blood drawing velocity during O-MAHT to see its effects on the vascular system and symptomatology. We administered O-MAHT to 11 subjects, and we interleaved fast and slow reinfusions. We monitored cerebral macrocirculation with transcranial Doppler (TCD) and tissue microcirculation with near-infrared spectroscopy (NIRS). Annoying symptoms appeared just during the fast reinfusion periods. NIRS and TCD parameters revealed vasoconstriction during fast reinfusion and improved metabolism during slow reinfusion. Overall, our investigation well discriminated fast from slow reinfusion velocity.

scholarly journals A closed audit reviewing the electrocardiograms of patients presenting to the memory assessment team

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S30-S30
Author(s):  
Joseph Heath ◽  
Maroulla Anderson ◽  
Jonathan Miles-Stokes
Keyword(s):  
Side Effects ◽  
Acetylcholinesterase Inhibitors ◽  
Left Ventricular ◽  
Cardiac Conduction ◽  
North West ◽  
Cardiac Side Effects ◽  
Memory Assessment ◽  
The North ◽  
Conduction Disorders ◽  
Clinically Significant

AimsTo review the ECGs of all patients referred to MAT services over the preceding 5 year period.BackgroundNeurodegenerative conditions such as Alzheimer's Disease can be treated with Acetylcholinesterase Inhibitors (AChEI) to slow down cognitive decline. Side effects of AChEIs include bradycardia, syncope and cardiac conduction disorders. An electrocardiograms (ECG) is completed prior to memory assessment team (MAT) medical assessments to screen for those who may be at risk of the cardiac side effects of AChEIs. ECGs may be included in the initial referral to the service or completed by the MAT. Given the predominantly elderly population referred to the MATs service, other incidental abnormalities are to be expected. Not all MAT referrals that are screened by memory nurses reach the threshold to be reviewed by the medical team and therefore not all ECGs are routinely reviewed, potentially missing clinically significant abnormalities.ResultA total of 1795 patients were identified as being referred to a single mental health unit in the North West on England over a five-year period. 781 (44%) of the patients had an ECG completed by the MAT, of which 452 (58%) showed an abnormality. Significant abnormalities that were previously unknown to the patients’ primary care provider include eight cases of Atrial Fibrillation (AF), four cases of Trifasciular Block, and 19 cases of Left Ventricular Hypertrophy (LVH). 64 (8%) of patients who had an ECG by the MAT had a bradycardia.ConclusionIn addition to identifying abnormalities that could interfere with memory medication, this audit showed that over half of the ECGs completed by the MAT had an atypical trace. Cardiology was consulted to identify which abnormalities were considered clinically significant and if not already known, the general practitioner (GP) was informed. A change in the local service means that all ECGs completed by the MAT are now screened at point of filling into the notes, so any future abnormalities are identified and followed up immediately.

Pharmacokinetics and Pharmacodynamics of Cisatracurium in Young and Elderly Adult Patients

1996 ◽  
Vol 84 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Shahpoor S. Sorooshian ◽  
Michael A. Stafford ◽  
Nigel B. Eastwood ◽  
Alastair H. Boyd ◽  
Christopher J. Hull ◽  
...  
Keyword(s):  
Muscle Relaxant ◽  
Time Course ◽  
Venous Blood ◽  
The Elderly ◽  
Adult Patients ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Elderly Adult ◽  
Elderly Adults ◽  
Duration Of Action

Background The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect. Methods Thirty-one young (18-50 yr) and 33 elderly ( > 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fetanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults. Results Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (ke0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05). Conclusions The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.

The Generation of Kinins in the Blood of Dogs during Hypotension Due to Haemorrhage

1970 ◽  
Vol 39 (3) ◽  
pp. 349-365 ◽  
Author(s):  
H. E. Berry ◽  
J. G. Collier ◽  
J. R. Vane
Keyword(s):  
Blood Pressure ◽  
Time Course ◽  
Venous Pressure ◽  
Venous Blood ◽  
Systemic Circulation ◽  
Substantial Effect ◽  
Mixed Venous Blood ◽  
Shed Blood ◽  
Arterial Blood ◽  
Organ Technique

1. Circulating kinins were detected and continuously assayed during hypotension due to haemorrhage in dogs, using the blood-bathed organ technique and isolated strips of cat jejunum as the assay tissue. 2. In arterial blood kinin concentrations of 1–5 ng/ml were attained after a hypotension of 35–65 mmHg had been maintained for 10–190 min. When portal venous blood was simultaneously assayed kinins appeared earlier and in concentrations 1–2 ng/ml higher than in arterial blood. No differences in time course of kinin generation or in concentration were found when mixed venous blood and arterial blood were compared. In those instances in which the blood pressure was restored to normal by returning the shed blood, kinin formation stopped. 3. Kinin generation was due to the presence in the circulation of a kinin-forming enzyme, such as kallikrein. When kallikrein was infused into the portal vein, it was partially inactivated by the liver. 4. Prolonged intravenous infusions of kallikrein (20–60 mu kg−1 min−1) generated kinins in the circulation in concentrations (1–5 ng/ml) which were well maintained throughout the infusion, demonstrating that kinin generation is not limited by depletion of the precursor kininogen; nevertheless, the effects of kallikrein infusions on the blood pressure and central venous pressure waned. 5. It is concluded that in hypotension due to haemorrhage, an active kallikrein appears in the portal circulation. Delay in the appearance of kallikrein in the systemic circulation may be due to the kallikrein inactivating mechanism of the liver. This inactivating mechanism may fail during shock. Kinins are generated in amounts sufficient to have a substantial effect on the circulation and an influence on the course of events in shock.

scholarly journals The Time Course of Inflammatory Biomarkers Following a One-Hour Exercise Bout in Canines: A Pilot Study

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 486
Author(s):  
Wendy Pearson ◽  
Julia Guazzelli Pezzali ◽  
Renan Antunes Donadelli ◽  
Ashley Wagner ◽  
Preston Buff
Keyword(s):  
Pilot Study ◽  
Time Course ◽  
Venous Blood ◽  
Exercise Bout ◽  
Exercise Stress ◽  
Moderate Intensity ◽  
Resolvin D1 ◽  
Moderate Intensity Exercise ◽  
Hunting Dogs ◽  
Inflammation Resolution

There is little information available to describe the inflammatory consequences of and recovery from moderate-intensity exercise bouts in hunting dogs. The purpose of the current study is to generate pilot data on the appearance and disappearance of biomarkers of inflammation and inflammation resolution following a typical one-hour exercise bout in basset hounds. Four hounds were set out to find a scent and freely adopted running or walking over wooded terrain for approximately one hour. Venous blood samples were obtained before the exercise and at 1, 2, 4, 6, and 10 h following cessation of exercise and were analyzed for biomarkers of inflammation (prostaglandin E2 (PGE2), nitric oxide (NO), interleukin 1β (IL-1β)) tumour necrosis factor-α (TNF-α)), and inflammation resolution (resolvin D1 (RvD1)). There was an increase in inflammation one hour after the exercise, shown by a significant increase in PGE2. Following this peak, PGE2 steadily declined at the same time as RvD1 increased, with RvD1 peaking at six hours. This pilot study provides evidence that dogs that undergo an hour of hunt exercise experience transient inflammation that peaks one hour after the end of exercise; inflammation resolution peaks six hours after the end of exercise. Future studies should seek to further understand the distinct and combined roles of PGE2 and RvD1 in dog adaptation to exercise stress.

Gas-blood Pco2 and Po2 equilibration in a steady-state rebreathing dog preparation

1984 ◽  
Vol 56 (5) ◽  
pp. 1229-1236 ◽  
Author(s):  
J. S. Clark ◽  
A. G. Cutillo ◽  
M. J. Criddle ◽  
D. V. Collins ◽  
F. L. Farr ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Steady State ◽  
Spontaneous Breathing ◽  
Time Course ◽  
Venous Blood ◽  
Inert Gas ◽  
Mixed Venous Blood ◽  
Gas Phases ◽  
Pulmonary Capillary ◽  
Pulmonary Capillary Blood

Alveolar gas and mixed venous blood PCO2 and PO2 were compared in a steady-state rebreathing dog preparation, during spontaneous breathing and mechanical ventilation, by a new null-balancing method that removes potential biases in the comparison of measurements in the blood and gas phases and includes an inert gas test to verify the equilibration between the rebreathing lung and the bag. No systematic PCO2 and PO2 differences were observed under equilibrium conditions. However, inert gas studies suggested that a high percentage of measurements obtained during spontaneous breathing were unreliable because of inadequate equilibration between blood and rebreathing bag (attributable to reduced ventilation or perfusion) and that all mechanical ventilation measurements were acceptable. The present data support the view that no PCO2 or PO2 gradients exist when the pulmonary capillary blood and alveolar gas are in equilibrium; the data also suggest that the steady-state rebreathing dog preparation may not be completely stable and that the time course of PCO2 and PO2 in the rebreathing bag may not be reliable as a means of assessing the equilibration between blood and bag.

scholarly journals Validation of an Enclosed Blood Collection System in a Pediatric Laboratory

2018 ◽  
Vol 3 (1) ◽  
pp. 65-78
Author(s):  
Elizabeth P Weinzierl ◽  
Cindy Brawley ◽  
James L Adams ◽  
Beverly B Rogers
Keyword(s):  
Clinical Laboratory ◽  
Blood Collection ◽  
Collection System ◽  
Current Collection ◽  
Tube Type ◽  
Clinically Significant ◽  
Almost All ◽  
Automated Instruments ◽  
Adult Volunteers ◽  
Transfer Device

Abstract Background Preanalytical, analytical, and postanalytical issues are often magnified in pediatric laboratories, and traditional vacuum-based blood tubes can contribute to some of these issues. Because of this, we investigated adopting an enclosed blood collection system that can perform vacuum or gentle aspiration blood collection, eliminating syringes, transfer device, and transfer steps, as well as potentially minimizing preanalytical error in the pediatric laboratory. We embarked on a validation of this tube system, in comparison with our current collection tubes, across most in-house tests at a large pediatric hospital. Methods Twenty adult volunteers were recruited. Blood was drawn into lithium heparin, serum, EDTA, and citrate tubes of each commercial tube type for comparison. For some tests, remnant blood from pediatric syringe draws was used when available. Samples were then processed and analyzed across all general areas of the clinical laboratory, and correlations of the results from the 2 tube systems were performed. Results Across 95 tests in the core laboratory and blood bank, almost all demonstrated clinically acceptable comparisons, with most R values >0.90. Only 3 of 95 tests demonstrated clinically significant differences between the tube systems. Conclusions Our validation of the enclosed blood collection system demonstrated acceptable results when compared with our current collection tubes. Additionally, with some minor modifications, our automated instruments could utilize ultralow-volume tubes from the enclosed blood collection system for direct tube sampling, which is impossible using our current small-volume tubes with our main chemistry analyzer.

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