scholarly journals SYNERGISTIC DRUG-DRUG INTERACTION;

2017 ◽  
Vol 24 (08) ◽  
pp. 1206-1210
Author(s):  
Aroosa Ishtiaq Butt ◽  
Bushra Tayyaba Khan ◽  
Zunera Hakim ◽  
Qamar-uz Zaman Khan
Keyword(s):  
Drug Interaction ◽  
Controlled Trial ◽  
Maximum Effect ◽  
Prokinetic Drug ◽  
Drug Drug Interaction ◽  
Group 2 ◽  
The Individual ◽  
Data Acquisition Unit ◽  
Randomised Controlled

Introduction: Ranitidine is known to us all as an anti-ulcer drug which acts byblocking H2 receptors in the stomach parietal cells. However its role in this category has beenunderstated. We studied its prokinetic effect on isolated duodenum of rabbits and its synergisticinteraction with Levosulpiride. The purpose of the study was to see if the two drugs do have aprokinetic effect and whether the combined effect is greater than the individual drugs. StudyDesign: Laboratory based Randomised controlled trial. Period: November 2014 to November2015. Setting: The study was carried out in the multidisciplinary laboratory at Army MedicalCollege after approval from Animals ethics committee. Material and methods: Dose responsecurve was constructed using cumulatively increasing concentrations of Ranitidine (Group 1)and Levosulpiride (Group 2). The synergistic prokinetic drug-drug interaction of Ranitidine andLevosulpiride was observed in Group 3 on iWorx Data acquisition unit (PowerLab). Resultsand Conclusion: Ranitidine produced a dose dependent reversible contraction of the isolatedduodenum and the maximum effect was recorded at 35 μg as 0.136 mV. Levosulpiride produceda maximum contraction of 0.088 mV at 70 μg. Ranitidine and levosulpiride curve was shifted tothe left and upwards of levosulpiride alone. The percent responses of levosulpiride alone was90 percent and with ranitidine was 122 percent. Ranitidine and levosulpiride have a synergisticprokinetic interaction in vitro. Conclusion: Ranitidine and levosulpiride have a synergisticprokinetic drug-drug interaction in vitro.

scholarly journals A randomised trial of rigid stump dressing following trans-tibial amputation for peripheral arterial insufficiency

2004 ◽  
Vol 28 (1) ◽  
pp. 22-27 ◽  
Author(s):  
K. R. Woodburn ◽  
S. Sockalingham ◽  
H. Gilmore ◽  
M. E. Condie ◽  
C. V. Ruckley
Keyword(s):  
Confidence Interval ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Randomised Trial ◽  
Significant Difference ◽  
Group 2 ◽  
Peripheral Arterial ◽  
The Individual ◽  
Post Trial ◽  
Randomised Controlled

Background: A multicentre randomised controlled trial to determine the effect of a rigid plaster dressing applied at the time of trans-tibial amputation on the number of days to casting for a prosthesis, and the incidence of post-operative stump infection. Methods: Patients requiring trans-tibial amputation were randomised to one of 2 groups: In Group 1 (intervention) a rigid above-knee plaster dressing was applied at operation and patients were managed according to a standard protocol. Group 2 (control) had the individual surgeons' usual non-rigid dressing regime. Rehabilitation data were extracted from the national physiotherapy database. On completion of the trial a questionnaire was sent to all participants. Results: 14 surgeons in 7 centres enrolled 154 patients, with 96 ultimately cast for a prosthesis. Patients who received a rigid dressing (n=78) had reduced days to casting (median 36, confidence interval 30–47) when compared with other dressings (n=76) (median 42, confidence interval 36–45), these differences did not reach statistical significance. There was no significant difference in post-operative infection rates in the two groups. 64% of surgeons, and all physiotherapists and vascular nurses responding to the post-trial questionnaire felt that the rigid dressing was an improvement on their normal regime and wished to continue with the technique. Conclusions: Despite a median reduction of 6 days in time to casting in patients treated with a rigid post-operative dressing this failed to reach statistical significance: The majority of participants who replied to the post-trial questionnaire expressed a wish to continue using the rigid dressing technique. To confirm that the trends shown in this trial are statistically valid a larger trial is needed.

The dolutegravir/valproic acid drug–drug interaction is primarily based on protein displacement

2021 ◽  
Author(s):  
P D J Bollen ◽  
H A B Prins ◽  
A Colbers ◽  
K Velthoven-Graafland ◽  
B J A Rijnders ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Drug Interaction ◽  
Controlled Trial ◽  
Underlying Mechanism ◽  
Hiv Rna ◽  
Parallel Increase ◽  
Drug Drug Interaction ◽  
To Receive ◽  
Protein Displacement

Abstract Objectives The dolutegravir/valproic acid drug–drug interaction (DDI) is suggested to be caused by protein displacement. Here, we assess the underlying mechanism. Methods Participants in a randomized controlled trial investigating valproic acid as an HIV latency reversing agent were recruited in a predefined pharmacokinetic substudy if they were on once-daily 50 mg dolutegravir-containing combination ART (cART) for >12 months with a plasma HIV-RNA <50 copies/mL (trial registration: ClinicalTrials.gov NCT03525730). Participants were randomized to receive 30 mg/kg/day valproic acid orally (divided into two equal doses) for 14 days or not. Total and unbound dolutegravir concentrations were measured on day 0 (before intake of valproic acid and 6 h after intake of valproic acid) and on days 1, 7, 14 and 42. Intra- and inter-subject dolutegravir concentrations and geometric means (GMs) were evaluated. Results Six of 10 participants on dolutegravir were randomized to receive valproic acid. During 14 days of valproic acid treatment, the GM total dolutegravir concentration decreased sharply from 1.36 mg/L on day 0 to 0.85, 0.31 and 0.20 mg/L on days 0, 1, 7 and 14, respectively, while total dolutegravir concentrations in the controls remained comparable during the same period: 1.27–1.49 mg/L. We observed a parallel increase in unbound dolutegravir fractions ranging from 0.39% to 0.58% during valproic acid administration, compared with 0.25% to 0.28% without valproic acid. Unbound dolutegravir concentrations were above the established in vitro EC90 value for unbound dolutegravir in 85% of the tested samples. Conclusions This study confirms protein displacement as the main mechanism for this DDI, although additional mechanisms might be involved too. If dolutegravir is taken with food, this DDI is probably not clinically relevant.

Pharmacokinetic Drug-drug Interaction of Antibiotics Used in Sepsis Care in China

2020 ◽  
Vol 21 ◽  
Author(s):  
Xuan Yu ◽  
Zixuan Chu ◽  
Jian Li ◽  
Rongrong He ◽  
Yaya Wang ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Penicillin G ◽  
Literature Mining ◽  
Human Pharmacokinetics ◽  
P450 Enzyme ◽  
Drug Drug Interaction ◽  
Pharmacokinetic Drug ◽  
Sepsis Care

Background: Many antibiotics have a high potential for having an interaction with drugs, as perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients. Methods: The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature mining was conducted to obtain human pharmacokinetics/dispositions of the antibiotics, their interactions with drug metabolizing enzymes or transporters, and their associated clinical drug interactions. Potential DDI is indicated by a DDI index > 0.1 for inhibition or a treated-cell/untreated-cell ratio of enzyme activity being > 2 for induction. Results: The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential drug interactions is summarized. Conclusion: Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole) and three lipophilic antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials (ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug transporters in vitro. Despite no reported clinical PK drug interactions with the transporters, caution is advised in the use of these antibacterials. Eight hydrophilic antibacterials (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin, ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims in drug interactions are scarce.

scholarly journals In vitro fertilisation (IVF) versus intracytoplasmic sperm injection (ICSI) in patients without severe male factor infertility: study protocol for the randomised, controlled, multicentre trial INVICSI

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e051058
Author(s):  
Sine Berntsen ◽  
Bugge Nøhr ◽  
Marie Louise Grøndahl ◽  
Morten Rønn Petersen ◽  
Lars Franch Andersen ◽  
...  
Keyword(s):  
Live Birth ◽  
Intracytoplasmic Sperm Injection ◽  
Controlled Trial ◽  
Male Partner ◽  
In Vitro Fertilisation ◽  
Male Factor Infertility ◽  
Male Factor ◽  
Fertilisation Rate ◽  
Randomised Controlled

IntroductionOver the last decades, the use of intracytoplasmic sperm injection (ICSI) has increased, even among patients without male factor infertility. The increase has happened even though there is no evidence to support that ICSI results in higher live birth rates compared with conventional in vitro fertilisation (IVF) in cases with nonmale factor infertility. The lack of robust evidence on an advantage of using ICSI over conventional IVF in these patients is problematic since ICSI is more invasive, complex and requires additional resources, time and effort. Therefore, the primary objective of the IVF versus ICSI (INVICSI) study is to determine whether ICSI is superior to standard IVF in patients without severe male factor infertility. The primary outcome measure is first live birth from fresh and frozen-thawed transfers after one stimulated cycle. Secondary outcomes include fertilisation rate, ongoing pregnancy rate, birth weight and congenital anomalies.Methods and analysisThis is a two-armed, multicentre, randomised, controlled trial. In total, 824 couples/women with infertility without severe male factor will be recruited and allocated randomly into two groups (IVF or ICSI) in a 1:1 ratio. Participants will be randomised in variable block sizes and stratified by trial site and age. The main inclusion criteria are (1) no prior IVF/ICSI treatment, (2) male partner sperm with an expected count of minimum 2 million progressive motile spermatozoa following density gradient purification on the day of oocyte pick up and (3) age of the woman between 18 and 42 years.Ethics and disseminationThe study will be performed in accordance with the ethical principles in the Helsinki Declaration. The study is approved by the Scientific Ethical Committee of the Capital Region of Denmark. Study findings will be presented, irrespectively of results at international conferences and submitted for publication in peer-reviewed journals.Trial registration numberNCT04128904. Pre-results.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

In vitro and in vivo Drug-Drug Interaction of Losartan and Glimepiride in Rats and Its Possible Mechanism

Pharmacology ◽  
2015 ◽  
Vol 95 (3-4) ◽  
pp. 133-138 ◽  
Author(s):  
Sai-Zhen Chen ◽  
Pei-Pei Pan ◽  
Shuang-Hu Wang ◽  
Jun Luo ◽  
Guo-Xin Hu ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Drug Interaction
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