Electroencephalograph variables, drug concentrations and sedation scores in children emerging from propofol infusion anaesthesia

In present investigation liquisolid compact technique is investigated as a tool for enhanced dissolution of poorly water-soluble drug Ketoconazole. The liquisolid tablets were formulated with liquid medications, namely Propylene Glycol (PG) drug concentrations, 60% w/w, 70% w/w and 80% w/w. Avicel pH102 was used as a carrier material, Aerosil 200 as a coating material and Sodium starch glycollate as a super-disintegrant. Quality control tests, such as uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate prepared tablets. For further confirmation of results the liquisolid compacts were evaluated by XRD and FTIR studies to prove that, solubility of Ketoconazole has been increased by liquisolid compact technique. From the results obtained, it was be speculated that such systems exhibit enhanced drug release profiles due to increased wetting properties and surface of drug available for dissolution. As liquisolid compacts demonstrated significantly higher drug release rates, in PG as compared to directly compressible tablets and conventional wet granulation, we lead to conclusion that it could be a promising strategy in improving the dissolution of poor water soluble drugs and formulating immediate release solid dosage forms.

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Methodological Approaches to Evaluate Fetal Drug Exposure

Current Pharmaceutical Design ◽

10.2174/1381612825666190319102812 ◽

2019 ◽

Vol 25 (5) ◽

pp. 496-504 ◽

Cited By ~ 7

Author(s):

Naïm Bouazza ◽

Frantz Foissac ◽

Déborah Hirt ◽

Saïk Urien ◽

Sihem Benaboud ◽

...

Keyword(s):

Cord Blood ◽

Drug Exposure ◽

Placental Transfer ◽

Ex Vivo ◽

Pharmacokinetic Analysis ◽

Population Pharmacokinetic ◽

Pbpk Models ◽

Drug Concentrations ◽

Fetal Drug Exposure

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies. Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure. Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results. Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.

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Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

Current Drug Metabolism ◽

10.2174/1389200221666200218121050 ◽

2020 ◽

Vol 21 (2) ◽

pp. 126-131

Author(s):

Bhuvanachandra Pasupuleti ◽

Vamshikrishna Gone ◽

Ravali Baddam ◽

Raj Kumar Venisetty ◽

Om Prakash Prasad

Keyword(s):

Plasma Concentration ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Plasma Concentrations ◽

Control Group ◽

Drug Concentrations ◽

Significant Difference ◽

Post Hoc ◽

Hydrolysis Of ◽

Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

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Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study

Current Drug Delivery ◽

10.2174/1567201818666210101112256 ◽

2021 ◽

Vol 18 ◽

Author(s):

Francine Rubião ◽

Alan Cezar Faria Araújo ◽

João Bernardo Sancio ◽

Bárbara Silva Nogueira ◽

Juçara Ribeiro Franca ◽

...

Keyword(s):

Ocular Hypertension ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

T Test ◽

Controlled Study ◽

Therapeutic Drug ◽

Eye Drops ◽

Open Angle ◽

Drug Concentrations

Background: The most common treatment for primary open-angle glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and ocular hypertension (OH). Methods: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, we used a two-way analysis of variance (ANOVA), Student t-test, and paired t-test. Results: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. Conclusions: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.

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Microextraction and Chromatographic Analysis of Budesonide Epimers in Exhaled Breath Condensate

Current Analytical Chemistry ◽

10.2174/1573411015666191203104522 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1032-1040

Author(s):

Laleh Samini ◽

Maryam Khoubnasabjafari ◽

Mohamad M. Alimorad ◽

Vahid Jouyban-Gharamaleki ◽

Hak-Kim Chan ◽

...

Keyword(s):

Biological Fluids ◽

Exhaled Breath Condensate ◽

Low Cost ◽

Exhaled Breath ◽

Chromatography Method ◽

Extraction Solvent ◽

Drug Concentrations ◽

Dispersive Liquid Liquid Microextraction ◽

Breath Condensate

Background: Analysis of drug concentrations in biological fluids is required in clinical sciences for various purposes. Among other biological samples, exhaled breath condensate (EBC) is a potential sample for follow up of drug concentrations. Methods: A dispersive liquid-liquid microextraction (DLLME) procedure followed by a validated liquid chromatography method was employed for the determination of budesonide (BDS) in EBC samples collected using a homemade setup. EBC is a non-invasive biological sample with possible applications for monitoring drug concentrations. The proposed analytical method is validated according to the FDA guidelines using EBC-spiked samples. Its applicability is tested on EBC samples collected from healthy volunteers receiving a single puff of BDS. Results: The best DLLME conditions involved the use of methanol (1 mL) as a disperser solvent, chloroform (200 μL) as an extraction solvent, and centrifugation rate of 3500 rpm for 5 minutes. The method was validated over a concentration range of 21-210 μg·L-1 in EBC. Inter- and intra-day precisions were less than 10% where the acceptable levels are less than 20%. The validated method was successfully applied for the determination of BDS in EBC samples. Conclusion: The findings of this study indicate that the developed method can be used for the extraction and quantification of BDS in EBC samples using a low cost method.

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Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190118120030 ◽

2019 ◽

Vol 19 (8) ◽

pp. 1037-1047 ◽

Cited By ~ 2

Author(s):

Jihene Elloumi-Mseddi ◽

Dhouha Msalbi ◽

Raouia Fakhfakh ◽

Sami Aifa

Keyword(s):

Side Effects ◽

Anticancer Drugs ◽

Tumour Cell ◽

Caspase 3 ◽

Drug Repositioning ◽

Brdu Incorporation ◽

Drug Concentrations ◽

Significant Difference ◽

Ic50 Values ◽

Mcf 7

Background:Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates.Objective:In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).Methods:Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity.Results:Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect.Conclusion:Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.

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Serum drug concentrations to optimize switching from adalimumab to etanercept in rheumatoid arthritis

Scandinavian Journal of Rheumatology ◽

10.1080/03009742.2019.1577915 ◽

2019 ◽

Vol 48 (4) ◽

pp. 266-270 ◽

Cited By ~ 2

Author(s):

MJ l’ Ami ◽

J Ruwaard ◽

CLM Krieckaert ◽

MT Nurmohamed ◽

RF van Vollenhoven ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Drug Concentrations

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Effects of Dexmedetomidine as an Analgesic Adjuvant for Surgery of Femur Fracture: A Systematic Review and Meta-Analysis

Pharmacology ◽

10.1159/000515788 ◽

2021 ◽

pp. 1-9

Author(s):

Shan Deng ◽

Yonghao Yu

Keyword(s):

Femur Fracture ◽

Meta Analysis ◽

Sensory Block ◽

Cochrane Library ◽

Rescue Analgesia ◽

Block Level ◽

Block Time ◽

Sedation Scores ◽

The Difference ◽

The Cochrane Library

Patients who undergo surgery of femur fracture suffer the excruciating pain. Dexmedetomidine (DEX) is a unique α2-adrenergic receptor agonist with sedative and analgesic properties, whose efficacy and safety are still unclear for surgery of femur fracture. Randomized controlled trials comparing the effects of addition of DEX to general or local anesthesia in surgery of femur fracture were searched from MEDLINE, EMBASE, and the Cochrane Library database. Patients who received DEX infusion had a significant longer time to rescue analgesia compared with those without DEX coadministration. DEX treatment seemed to reduce the visual analog score; however, the significance did not reach any statistical difference. DEX as an analgesic adjuvant did not reduce the onset of sensory block time, shorten the time to achieve maximum sensory block level, and provide a longer duration of sensory block. The difference in mean sedation scores between 2 groups was not statistically significant. As for adverse effects, DEX therapy significantly increased the rate of hypotension. In conclusion, dexmedetomidine as a local anesthetic adjuvant in femur fracture surgery had a longer duration of rescue analgesia. However, the incidence of hypotension was markedly increased in these patients. It was worth noting that the evidence was of low to moderate quality.

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A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.154 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 162-163

Author(s):

M Mikail ◽

A Wilson

Keyword(s):

Inflammatory Bowel Disease ◽

Pyoderma Gangrenosum ◽

Bowel Disease ◽

Complete Resolution ◽

Therapeutic Drug ◽

Drug Concentrations ◽

Median Serum ◽

Inflammatory Bowel ◽

Factor Α ◽

Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

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