SUBCUTANEOUS AND INTRAVENOUS ADMINISTRATION OF DESMOPRESSIN (DDAVP) TO HEMOPHILIACS: PLASMA PHARMACOKINETICS AND FACTOR VIII (VIII:C) RESPONSES

1987 ◽  
Author(s):  
P M Mannucci ◽  
V Vicente ◽  
I Alberca ◽  
E Sacchi ◽  
A S Harris ◽  
...  
Keyword(s):  
Hemophilia A ◽  
The Body ◽  
Intravenous Route ◽  
Maximum Increase ◽  
Time Curve ◽  
Patient Response ◽  
Routes Of Administration ◽  
Time To Peak ◽  
Rate Of Absorption ◽  
Plasma Pharmacokinetics

Reported studies dealing with the clinical use of DDAVP in mild and moderate hemophilia A patients show a very large between-patient variability for the maximum increase of VIII:C after the drug given intravenously (i.v.) or subcutaneously (s.c.). By measuring DDAVP plasma levels with a sensitive and specific RIA method, we elected to evaluate whether or not between-patient response variability was related to the variability of DDAVP levels achieved in their plasma. To this purpose 14 moderate or mild hemophilic volunteers (baseline VIII : C 4 to 31 U/dL) were randomly given 0.3 pg/Kg of i.v. or s.c. DDAVP with a between-treatment interval of 15 - 30 days. Plasma DDAVP pharmacokinetics in relation to the routes of administration are shown in the table.Pack levels (Cmax) were higher after i.v. DDAVP (p < 0.02). Time to peak levels (tmax) was shorter for i.v. DDAVP (p < 0.001). There was no difference between i.v. and s.c. DDAVP for plasma time curve (AUC) and half-life (t½).The bioavailability of the s.c. route relative to the i.v. route was 85 ° 32%. Of further interest, was the greater variability of the i.v. pharmacokinetics compared to the s.c. data. These differences were reflected in the VIII:C response. Maximum VIII:C increase over baseline levels was 3.2 ° 2.4 fold (i.v.) and 3.2 ° 1.3 fold (s.c.) (n.s.).Thus the i.v. route gave a marginally greater response but the effect was more variable than the s.c. route. Finally, no significant correlation was found between the VIII:C response and plasma DDAVP levels for either route of administration (i.v. route r = 0.03, s.c. route r = 0.23).These findings establish the subcutaneous route to be bioequivalent in effect to the intravenous route with less variation. This study also demonstrates that the VIII:C response to DDAVP is neither a function of the rate of absorption of the corrpound into the body nor the magnitude of the plasma concentration.

scholarly journals Design and Verification of a Reloadable Adrenaline Auto-Injector for Intramuscular Injections

2018 ◽  
Author(s):  
Gokul Nair ◽  
Michael Levin ◽  
Sudesh Sivarasu
Keyword(s):  
Vastus Lateralis ◽  
Gluteus Maximus ◽  
The Body ◽  
Severe Allergic Reaction ◽  
Vastus Lateralis Muscle ◽  
Routes Of Administration ◽  
Organ Systems ◽  
Rate Of Absorption ◽  
Critical Organ ◽  
Auto Injector

Anaphylaxis is a severe allergic reaction when a patient is exposed to an antigen to which they have become hypersensitive. Exposure to these antigens results in the release of mediators from mast cells in the body, causing inflammation of critical organ systems. Without immediate treatment, it can lead to patient mortality within 15 minutes. To increase the probability of patient survival, a dose of adrenaline must be administered. There are several routes of administration, but the use of an Adrenaline Auto Injector is the safest, quickest and most efficient route. An Adrenaline Auto-Injector (AAI) is an injection device that delivers adrenaline to the deep muscle tissue of the body, preferably via the vastus lateralis muscle (as the rate of absorption is more effective than other injection sites such as the deltoid, gluteus maximus etc). Adrenaline Auto-Injectors are preferable to syringes, or prefilled syringes as they are easier to use, and can be used by people that are not medically trained. They can also be used in highly stressful situations without much risk of injury.

Effect of Antacid on Bioavailability of a Sustained-Release Theophylline Preparation

1983 ◽  
Vol 17 (7-8) ◽  
pp. 555-557 ◽  
Author(s):  
Lazarus J. Darzentas ◽  
Ronald B. Stewart ◽  
Stephen H. Curry ◽  
Richard L. Yost
Keyword(s):  
Serum Concentration ◽  
Sustained Release ◽  
High Potency ◽  
Time Curve ◽  
Time To Peak ◽  
Sustained Release Theophylline ◽  
Study Interval ◽  
Rate Of Absorption ◽  
Theophylline Absorption ◽  
Tablet Preparation

The effect of coadministration of an antacid on bioavailability of a sustained-release theophylline tablet preparation (Theo-Dur) was studied by crossover comparison in five young, healthy, nonsmoking volunteers. Water 90 ml, or “high potency” aluminum-magnesium hydroxide antacid (Mylanta II) 10 ml and water 80 ml were administered concurrently with sustained-release theophylline 600 mg. Eleven blood samples were collected over the next 24 hours. Serum was analyzed with high pressure liquid chromatography technique to determine theophylline concentration. Peak serum concentration (Cmax) and time to peak concentration (tmax) were determined, and area under the 24-hour serum concentration-time curve (AUC) was calculated by the trapezoidal rule for each subject at each study interval. The Student's paired t-test was used to compare Cmax, tmax, and AUC for both treatments. A uniform difference was found between groups in Cmax. Cmax was higher in subjects when treated with the antacid (10.45 ± 3.03 vs. 8.30 ± 2.90 μg/ml, p < 0.05) than when given theophylline alone. The mean tmax for the two treatments did not differ (10.4 ± 1.67 h—combination vs. 10.8 ± 1.1 h—theophylline, p > 0.05). Likewise, mean AUC was unchanged by the coadministration of antacid (140.65 ± 41.6 μg/ml·h—combination vs. 155.13 ± 46.6 μg/ml·h—theophylline, p > 0.05). The use of a high-potency antacid product did not decrease the extent of theophylline absorption from this sustained-release product, but did increase Cmax and, presumably, rate of absorption. High-potency aluminum-magnesium antacids can probably be used in combination with this sustained-release theophylline tablet without detriment to therapy.

scholarly journals Impact of type 2 diabetes mellitus on left ventricular diastolic function in patients with essential hypertension: evaluation by volume-time curve of cardiac magnetic resonance

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Wei-feng Yan ◽  
Yue Gao ◽  
Yi Zhang ◽  
Ying-kun Guo ◽  
Jin Wang ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Diastolic Function ◽  
Control Group ◽  
Peak Strain ◽  
Filling Rate ◽  
Time Curve ◽  
Time To Peak ◽  
Peak Ejection Rate ◽  
Lv Diastolic Dysfunction

Abstract Background Essential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR). Methods A total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters. Results PFR and PFR/EDV decreased from the control group, through HTN(T2DM −), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM −) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM −) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (β = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = − 0.756 ~ 0.795). Conclusions T2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.

scholarly journals Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
The Body ◽  
Intralesional Injection ◽  
Intraarterial Infusion ◽  
Routes Of Administration ◽  
Administration Routes

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.

Control of Rapidly Executed Forces to a Target

1987 ◽  
Vol 65 (3) ◽  
pp. 827-836
Author(s):  
Donald Siegel
Keyword(s):  
Visual Feedback ◽  
Predictor Variable ◽  
Peak Force ◽  
Important Predictor ◽  
Force Amplitude ◽  
Time Curve ◽  
Time To Peak ◽  
Hand Grip ◽  
Rapid Responses ◽  
Force Time

The purpose of the present study was to determine whether initial measures of impulse (i.e., area under the force-time curve) could be used to predict peak force (PF) in hand grip responses of 5- and 10-kg amplitude executed as rapidly as possible. 12 subjects performed 75 practice and 25 test contractions in each condition, with and without visual feedback. The time to peak (PT) for the 5-kg responses was 41 msec., while the 10-kg condition averaged 56 msec. Analyses demonstrated no effect for visual feedback. Correlational analyses of cumulative impulse sections from 5 msec., to PF within conditions showed that early measures of force within a response were not very good predictors of final force amplitude. Indeed, for both conditions upwards of 85% of a reponse needed to have occurred before 50% of PF variance could be predicted. Analyses across conditions demonstrated that 50% of PF variance could be predicted between 15 and 20 msec. PT was also an important predictor variable. By using PT along with cumulative impulse 50% of the variance in PF could be predicted prior to 10 msec., at 5 kg (25% of PT) and at about 15 msec., for 10 kg (27% of PT). Across conditions, 85% of the variance in PF was predictable by 5 msec. Such results suggest that either more refined response indices are needed in predicting response outcome or that even for very rapid responses some lower level “tuning” probably occurs after initiation.

scholarly journals Herb-Drug Interaction betweenEchinacea purpureaand Darunavir-Ritonavir in HIV-Infected Patients

2010 ◽  
Vol 55 (1) ◽  
pp. 326-330 ◽  
Author(s):  
José Moltó ◽  
Marta Valle ◽  
Cristina Miranda ◽  
Samandhy Cedeño ◽  
Eugenia Negredo ◽  
...  
Keyword(s):  
High Performance ◽  
Geometric Mean ◽  
Echinacea Purpurea ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Root Extract ◽  
Open Label ◽  
Fixed Sequence ◽  
Time Curve ◽  
Sequence Study

ABSTRACTThe aim of this open-label, fixed-sequence study was to investigate the potential ofEchinacea purpurea, a commonly used botanical supplement, to interact with the boosted protease inhibitor darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy including darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included.E. purpurearoot extract capsules were added to the antiretroviral treatment (500 mg every 6 h) from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavir-ritonavir on days 0 (darunavir-ritonavir) and 14 (darunavir-ritonavir plus echinacea). Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 with the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 49 (range, 43 to 67) years, and the body mass index was 24.2 (range, 18.7 to 27.5) kg/m2. Echinacea was well tolerated, and all participants completed the study. The GMR for darunavir coadministered with echinacea relative to that for darunavir alone was 0.84 (90% CI, 0.63-1.12) for the concentration at the end of the dosing interval, 0.90 (90% CI, 0.74-1.10) for the area under the concentration-time curve from 0 to 12 h, and 0.98 (90% CI, 0.82-1.16) for the maximum concentration. In summary, coadministration ofE. purpureawith darunavir-ritonavir was safe and well tolerated. Individual patients did show a decrease in darunavir concentrations, although this did not affect the overall darunavir or ritonavir pharmacokinetics. Although no dose adjustment is required, monitoring darunavir concentrations on an individual basis may give reassurance in this setting.

Theoretical foundations and general provisions of autohemotherapy

1930 ◽  
Vol 26 (7) ◽  
pp. 118-124
Author(s):  
S. I. Sherman
Keyword(s):  
Morphological Changes ◽  
Scientific Basis ◽  
The Body ◽  
Practical Medicine ◽  
Routes Of Administration ◽  
Therapeutic Measures ◽  
Theoretical Foundations ◽  
Dosage Frequency

Currently, autohemotherapy takes one of the places of honor among; of our therapeutic measures and there is not a single area of ​​practical medicine where oisch is not applied. At the same time, this type of therapy still does not have an exact scientific basis; Thus, there are many different views on the essence of the action of this method, but there are still no precise indications and contraindications for the use of autohemotherapy for certain types of diseases, then the dosage, frequency of injections, their number, etc., vary sharply among different authors. we will review the following issues - the essence of the action of autohemotherapy, the dosage and frequency of injections, the reaction of the body (general, focal, local), the advantage of one or another method of using autoblood injections (intracutaneous, subcutaneous and intramuscular routes of administration) and, finally, morphological changes in blood during this method of treatment.

Fabrication of α-TCP, HAp Functionally Graded Porous Beads

2008 ◽  
Vol 57 ◽  
pp. 135-138
Author(s):  
Yuji Kajihata ◽  
Teruo Asaoka ◽  
Katsuko S. Furukawa ◽  
Takashi Ushida ◽  
T. Tateishi
Keyword(s):  
Surface Layer ◽  
High Strength ◽  
Functionally Graded ◽  
The Body ◽  
Acid Solutions ◽  
Bioactive Material ◽  
Hydrolytic Reaction ◽  
Rate Of Absorption ◽  
Porous Beads ◽  
Good Cell

HAp (Hydroxyapatite) and α-TCP (alpha tribasic calcium phosphate) are non-toxic to human cells and, thus, have been studied for applications as biomaterials. HAp is a bioactive material that is not readily absorbed by the body; it offers both high strength and better tissueadhesive properties than α-TCP. In contrast, α-TCP is highly bioabsorbable; it is quickly absorbed by the body, and, therefore, for example, disappears before bone is completely replaced. If porous beads could be fabricated that would take advantage of the useful properties of α-TCP and HAp, they could be used as excellent scaffolds for cultivating cells. In the present study, ceramic beads with α-TCP at the center were fabricated and coated with a functionally graded film of HAp. A scaffold based on this configuration would be expected to have the following characteristics: good cell adhesion; strong beads; and a rate of absorption into the body that would be easy to control. In addition, to accelerate the formation of porous structure, some acid solutions were used to dissolve the beads surface layer and to penetrate pores toward inside of the bead. HAp formation through hydrolytic reaction seemed to be promoted by these acid solutions.

THE MANAGEMENT OF THE CRITICALLY ILL CHILD WITH DEHYDRATION SECONDARY TO DIARRHEA

PEDIATRICS ◽  
1970 ◽  
Vol 45 (6) ◽  
pp. 1029-1036
Author(s):  
Laurence Finberg
Keyword(s):  
Diarrheal Disease ◽  
Oral Intake ◽  
The Body ◽  
Critical Stage ◽  
Water Losses ◽  
Subcutaneous Infusion ◽  
Routes Of Administration ◽  
Parenteral Route ◽  
Trained Personnel ◽  
Enteric Infections

Diarrhea and vomiting, which so frequently complicate diarrheal diseases, occur in a variety of disorders affecting infants. Although enteric infections cause these symptoms more often than all other diseases combined, noninfectious causes may occasionally also occur. While each cause may have specific other effects, the discussion here will deliberately be limited to the management of the physiologic disturbances that accompany excessive loss of water and salts from tile gastrointestinal tract. Etiologic considerations, however important they may be, will not be further pursued. This emphasis is appropriate since survival following critical dehydration depends far more upon the correction of the physiologic disturbance than upon the removal of the cause. A critical stage in diarrheal disease may be defined as occurring when a volume of fluid equal in mass to about 10% of the body weight has been lost over a period of a day or two. Clinically, this usually occurs shortly after anorexia or vomiting has precluded oral intake. At this stage of illness, parenteral fluid therapy should be employed. Oral intake should be curtailed during the early hours of therapy. The use of milk or other foods high in calories and solute complicates management by markedly increasing stool water losses. Even if severe undernutrition coexists with tile diarrhea, the first 6 to 8 hours should be a period of brief starvation; the parenteral glucose will provide emergency calories. Although such routes of administration as intragastric drip and subcutaneous infusion have been employed successfully, their usage should be restricted to places where a deficiency of supplies or trained personnel interdicts the preferred parenteral route—continuous intravenous infusion.

Prognostic Significance of CHEK2 Mutation in Progression of Breast Cancer

2019 ◽  
Vol 50 (3) ◽  
pp. e36-e41
Author(s):  
Narges Ansari ◽  
Saeid Shahrabi ◽  
Abbas Khosravi ◽  
Reza Shirzad ◽  
Hadi Rezaeean
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Cell Signaling ◽  
Prognostic Significance ◽  
The Body ◽  
Response To Treatment ◽  
Patient Response ◽  
Disease Mutations ◽  
Detection Of Mutations ◽  
Cell Signaling Pathways

Abstract Breast cancer (BC) is one of the most common cancers among women; genetic mutations reflect the development of this disease. Mutations in cell signaling factors can be the main cause of BC development. In this study, we focused on mutations in checkpoint kinase 2 (CHEK2) and their impact as a prognostic factor in the pathogenesis of BC. CHEK2 is controlled in cell signaling pathways through the influence of upstream genes. Also, several downstream genes are regulated by CHEK2. In addition, mutations in CHEK2 lead to resistance of BC cells to chemotherapy and metastasis of cancer cells to other parts of the body. Finally, detection of mutations in CHEK2 can be used as a prognostic factor for patient response to treatment and for targeting downstream molecules of CHEK2 that are involved in the proliferation of breast tumor cells. Mutations such as c.1100delC and I157T can distinguish which patients are susceptible to metastasis.

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