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Pharmacokinetics of controlled release morphine (MST) in patients with liver cirrhosis

Research Abstract

We have studied the kinetic profile of controlled release morphine (MST) in 12 patients with posthepatitic cirrhosis, caused by HCV and HBsAg, with portal hypertension, given MST 30 mg for endoscopic sclerotherapy and compared the data with those from 10 healthy controls. Plasma drug concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography (HPLC). Total body clearance (Cl) and systemic availability were estimated using a compartmental method. Patients with cirrhosis had less clearance (0.586 litre h-1) than controls (0.729 litre h-1). Mean residence time (MRT) was prolonged in cirrhotic patients (19.57 h) compared with controls (7.03 h). Elimination half-life in cirrhotic patients (mean 7.36 (SEM 0.45) h) was nearly twice that of controls (4.01 (0.15) h). Serum concentrations were higher at all sampling times in the cirrhotic patients (peak concentration 35.2 (3.2) ng ml-1 compared with 12.8 (0.4) ng ml-1 in controls). For these changes in the kinetic profile of morphine (as MST) in cirrhotic patients, who experienced more sedation than controls, a smaller dose study together with longer dosing intervals is recommended.

Research Authors
HI Kotb, MY El-Kabsh, SE Emara, EA Fouad
Research Date
Research Department
Research Journal
British journal of anesthesia
Research Member
Research Publisher
science direct
Research Vol
79
Research Website
DOI: 10.1093/bja/79.6.804
Research Year
1997

Pharmacokinetics of oral tramadol in patients with liver cancer.

Research Abstract

Background: There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world.
Methods: The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. All pharmacokinetic variables were evaluated using one-compartment model.
Results: Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 μg/h/L (SD = 41), 1,327 μg/h/L (SD = 51), 1,138.5 μg/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period.
Conclusion: It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe.

Research Authors
HI Kotb, IA Fouad, KM Fares, MG Mostafa, AER AM
Research Date
Research Department
Research Journal
Journal of opioid management
Research Member
Research Publisher
Weston Medical Publishing
Research Vol
4
Research Website
DOI: https://doi.org/10.5055/jom.2008.0014
Research Year
2008

The effect of rectal ozone on the portal vein oxygenation and pharmacokinetics of propranolol in liver cirrhosis (a preliminary human study)

Research Abstract

Aim: The aim of this study was to investigate the effect of rectal ozone on portal vein oxygenation and the pharmacokinetic changes of propranolol in patients with liver cirrhosis.

Methods: Fifteen patients with liver cirrhosis were included They were given a fixed oral dose of propranolol 80mg on the morning of day 1 after overnight fasting. Blood samples were collected at fixed time intervals for 24h. Patients were given 12 sessions of rectal ozone of 300ml of 40% ozone/oxygen mixture. On day 14 another oral dose of 80mg propranolol was given and blood samples were collected as on day 1. Plasma concentrations of propranolol were measured by HPLC. Portal vein oxygen tension and saturation were measured before and after rectal ozone.

Results: Plasma concentrations of propranolol were reduced after ozone therapy with pronounced decreases in the maximum plasma concentration and the area under the plasma concentration-time curve. The changes were consistent with a decrease in propranolol bioavailability. There was a decrease in the elimination half-life and mean residence time. Portal vein oxygenation significantly increased after rectal ozone.

Conclusions: The changes in the pharmacokinetics of propranolol probably reflect an increase in the rate and extent of its metabolism resulting from improved portal vein oxygenation attributable to the ozone therapy. The present work highlights that ozone can be an alternative medical measure to improve portal vein oxygenation in liver cirrhosis.

Research Authors
S Zaky, EA Fouad, HIM Kotb
Research Date
Research Journal
British journal of clinical pharmacology
Research Member
Research Publisher
British pharmacological society
Research Vol
71
Research Website
DOI: 10.1111/j.1365-2125.2010.03851.x
Research Year
2011

Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma

Research Abstract

Background: There are no studies reported on the pharmacokinetics of controlled release morphine (MST) in patients with hepatocellular carcinoma, the fifth most common cancer in the world.

Methods: We have studied the pharmacokinetic profile of MST (30 mg) in 15 patients with liver carcinoma (eight with primary carcinoma on top of chronic hepatitis C, and seven with secondary metastatic liver malignancy as a result of other primary) compared with our previously published data for 10 healthy controls. Plasma morphine concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography. Total body clearance (Cl) and systemic bioavailability were estimated using a compartmental method.

Results: Morphine bioavailability showed a substantial increase in patients with primary liver and secondary metastatic carcinoma than that of controls (64.8, 62.1, and 16.8%, respectively). The area under the serum concentration-time curve increased 4-fold in primary carcinoma (416 [sem25] microg h(-1) litre(-1)) and 3-fold (303 [21] microg h(-1) litre(-1)) in metastatic liver patients compared with healthy control (92.5 [3] microg h(-1) litre(-1)). No significant difference was found in T(max) between the two malignant groups but C(max) was significantly greater in primary liver carcinoma patients. Impaired morphine elimination was noted in primary carcinoma only (t(1/2) 5.99 [0.39] h).

Conclusion: Careful administration of morphine is recommended in patients with liver cancer.

Research Authors
HIM Kotb, SA El-Kady, SES Emara, EA Fouad, MY El-Kabsh
Research Date
Research Journal
British journal of anesthesia
Research Member
Research Publisher
science direct
Research Vol
94
Research Website
doi: 10.1093/bja/aei007. Epub 2004 Oct 29.
Research Year
2005

Formulation design of indomethacin-loaded nanoemulsion for transdermal delivery

Research Abstract
The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery
of indomethacin (IND). Nanoemulsions formulations with different Surfactant: co surfactant ratios (S mix); F1-F6
(1:1, 2:2, 3:1, 4:1, 1:2 and 3:2) were prepared by the spontaneous emulsification method, and characterized for
morphology using transmission electron microscopy (TEM), droplet size, and rheological characteristics. The ex
vivo skin permeation studies were performed using Franz diffusion cell with rabbit skin as permeation membrane. A
significant increase in the permeability parameters such as steady-state flux (Jss), permeability coefficient (Kp), and
enhancement ratio (Er) was observed in nanoemulsion formulations compared with the conventional IND gel. The
anti-inflammatory effects of nanoemulsion formulations showed a significant increase in percent inhibition value after
4 hours when compared with conventional IND gel on carrageenan-induced paw edema in rats. Significant increase
in permeability parameters was observed in nanoemulsion formulations (P< 0.05). The steady-state flux (Jss) and
permeability coefficient (Kp ) for optimized nanoemulsion formulation (F1 , 1:1 S mix were found to be 22.61±3.45 μg/
cm2 /h and 0.22x10− 2 ±0.0003 cm/h, respectively), which were significant compared with conventional IND gel and
(P< 0.001). Enhancement ratio (Er ) was found to be 8.939 in optimized formulation F1 compared with IND gel.
These results suggested that nanoemulsions can be used as potential vehicles for improved transdermal delivery of
indomethacin as an approach to eliminate the side effect of the oral dose
Research Authors
N Barakat, E Fouad, A Elmedany
Research Date
Research Department
Research Journal
Pharm Anal Acta
Research Member
Research Publisher
Walsh medical media
Research Vol
2
Research Website
DOI: Pharm Anal Acta 2011, S2 10.4172/2153-2435.S2-002
Research Year
2011

The Faculty of Pharmacy - Assiut University announces the holding of a symposium entitled “Equal Opportunities and Women’s Empowerment.”

Within the framework of cooperation between the university’s faculties and benefiting from the transfer of expertise, the Faculty of Pharmacy - Assiut University announces the holding of a symposium entitled (Equal Opportunities and Women’s Empowerment)

Lecturing by Dr. Abdel Hakim Radwan Saeed - Assistant Professor at the Faculty of Education - Assiut University

Please participate on Wednesday, June 12, 2024, at eleven in the morning.

In the celebration hall - ground floor - Building (B) of the faculty

news category
خبر عام

Pharmaceutical interventions for drug-related problems in the neonatal intensive care unit incidence, types, and acceptability

Research Abstract

Background: Drug-related problems (DRPs) are widespread in hospitalized neonates, but studies on the prevalence of DRPs in this population are limited. The presence of clinical pharmacists on multidisciplinary teams helps prevent and reduce DRPs. Aim: This investigation aimed to identify and classify the incidence of DRPs in the neonatal intensive care unit (NICU), to determine the determining factors associated with DRPs and to document clinical pharmacists' interventions, outcomes, acceptance rates and clinical significance. Method: A prospective descriptive hospital study was conducted from August to November 2023 at the NICU of Children's University Hospital, Assiut University, Egypt. DRPs were classified using the Pharmaceutical Care Network of Europe (PCNE) classification V9.1. Results: Three hundred sixteen neonates were included in the study, with a mean gestational age of 34 ± 4 weeks and a mean birth weight of 2.03 ± 0.85 kg. A total of 1723 DRPs occurred among 283 neonates (89.6%), an average of 5.5 ± 5.1 DRPs per patient. The main types were treatment effectiveness (P1) (799, 46.4%), followed by others (P3) (469, 27.2%), and treatment safety (P2) (455, 26.4%). The leading causes were dose selection (C3) (1264, 61.9%) and "other domain" (C9) (543, 26.6%). Of the 2149 interventions introduced by pharmacists, 98.8% were accepted and 93% were accepted, and fully implemented. As a result, 92% of the DRPs were resolved. Both length of hospital stay and number of medications were significantly associated with DRPs. Conclusion: DRPs are common in the NICU; this study demonstrated the crucial role of clinical pharmacists in identifying and resolving DRPs.

Research Authors
Norhan Attia Ahmed , Ehab Ahmed Fouad, Osama M El-Asheer, A S M Ghanem
Research Date
Research Department
Research Journal
Front Pharmaco
Research Member
Research Publisher
Frontiers
Research Vol
15
Research Website
doi: 10.3389/fphar.2024.1391657. eCollection 2024.
Research Year
2024

Editorial: Advances in metabolism and chemodiversity - focus - plant enzymes

Research Abstract

Plant enzymes are indispensable for plant metabolism and are critical determinants of the extensive chemodiversity observed in plants. These enzymes serve as primary catalysts in biosynthetic pathways, enabling the biosynthesis of a diverse range of secondary metabolites, such as alkaloids, terpenes, and phenolics. These metabolites are essential for the distinctive sensory qualities of plants, e.g., flavors, scents, and colors, and they also possess significant biological activities with promising applications in agriculture, medicine, and industry. Recent scientific investigations have been devoted to unraveling the intricate biochemistry of enzymes in photosynthetic organisms, elucidating their catalytic

Research Authors
Zhi-Yan Du, Yang Qu, Yang Qu, Zhenhua Liu, Zhenhua Liu, Mariam Gaid
Research Date
Research Image
Research Journal
Frontiers in Plant science
Research Member
Research Publisher
Frontiers
Research Rank
4.1
Research Vol
14
Research Website
https://doi.org/10.3389/fpls.2023.1227424
Research Year
2023

Comparative Bioremediation of Tetradecane, Cyclohexanone and Cyclohexane by Filamentous Fungi from Polluted Habitats in Kazakhstan

Research Abstract

Studying the fates of oil components and their interactions with ecological systems is essential for developing comprehensive management strategies and enhancing restoration following oil spill incidents. The potential expansion of Kazakhstan’s role in the global oil market necessitates the existence of land-specific studies that contribute to the field of bioremediation. In this study, a set of experiments was designed to assess the growth and biodegradation capacities of eight fungal strains sourced from Kazakhstan soil when exposed to the hydrocarbon substrates from which they were initially isolated. The strains were identified as Aspergillus sp. SBUG-M1743, Penicillium javanicum SBUG-M1744, SBUG-M1770, Trichoderma harzianum SBUG-M1750 and Fusarium oxysporum SBUG-1746, SBUG-M1748, SBUG-M1768 and SBUG-M1769 using the internal transcribed spacer (ITS) region. Furthermore, microscopic and macroscopic evaluations agreed with the sequence-based identification. Aspergillus sp. SBUG-M1743 and P. javanicum SBUG-M1744 displayed remarkable biodegradation capabilities in the presence of tetradecane with up to a 9-fold biomass increase in the static cultures. T. harzianum SBUG-M1750 exhibited poor growth, which was a consequence of its low efficiency of tetradecane degradation. Monocarboxylic acids were the main degradation products by SBUG-M1743, SBUG-M1744, SBUG-M1750, and SBUG-M1770 indicating the monoterminal degradation pathway through β-oxidation, while the additional detection of dicarboxylic acid in SBUG-M1768 and SBUG-M1769 cultures was indicative of the fungus’ ability to undertake both monoterminal and diterminal degradation pathways. F. oxysporum SBUG-M1746 and SBUG-M1748 in the presence of cyclohexanone showed a doubling of the biomass with the ability to degrade the substrate almost completely in shake cultures. F. oxysporum SBUG-M1746 was also able to degrade cyclohexane completely and excreted all possible metabolites of the degradation pathway. Understanding the degradation potential of these fungal isolates to different hydrocarbon substrates will help in developing effective bioremediation strategies tailored to local conditions.

Research Authors
Mariam Gaid* , Wiebke Jentzsch , Hannah Beermann , Anne Reinhard , Mareike Meister, Ramza Berzhanova, Togzhan Mukasheva, Tim Urich and Annett Mikolasch*
Research Date
Research Journal
Journal of Fungi
Research Member
Research Publisher
MDPI
Research Rank
4.2
Research Vol
10
Research Website
https://doi.org/10.3390/jof10060436
Research Year
2024
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