The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications.

The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications.

The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications.

The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross-sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high-dose amoxicillin/clavulanate (10-12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3-4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3-7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over-anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients' medications is necessary to avoid complications.

The aim of this study was to improve the bioavailability of water-insoluble, anti-emetic drug; domperidone (DMP) which has a poor oral bioavailability (13-17%) due to its extensive first pass metabolism. Solid dispersions of DMP with pluronic F-68 were prepared at different weight ratios by fusion method and they were tested for their in-vitro dissolution rate to select the best ratio for tablet formulation. Then, the selected solid dispersions were incorporated into sublingual tablets together with different water-soluble excipients. Sublingual tablets were prepared by direct compression technique and they were evaluated for their physical properties and in-vitro dissolution rate. Sublingual tablets formulae S4 (containing fructose and 10% w/w Ac-Di-Sol) and S8 (containing fructose and 10% w/w Explotab) showed the best results and thus; they were selected for in-vivo studies in rabbits in comparison with the commercially-available oral tablets; Motinorm®. The selected formulae showed marked enhancement of DMP bioavailability compared with the marketed oral tablets, with relative bioavailability values of 432.49 ±10.13% and 409.32 ±11.59 % for S4 and S8, respectively. The results confirmed that sublingual tablets were promising tool for DMP delivery with marked enhancement of bioavailability.

The aim of this study was to improve the bioavailability of water-insoluble, anti-emetic drug; domperidone (DMP) which has a poor oral bioavailability (13-17%) due to its extensive first pass metabolism. Solid dispersions of DMP with pluronic F-68 were prepared at different weight ratios by fusion method and they were tested for their in-vitro dissolution rate to select the best ratio for tablet formulation. Then, the selected solid dispersions were incorporated into sublingual tablets together with different water-soluble excipients. Sublingual tablets were prepared by direct compression technique and they were evaluated for their physical properties and in-vitro dissolution rate. Sublingual tablets formulae S4 (containing fructose and 10% w/w Ac-Di-Sol) and S8 (containing fructose and 10% w/w Explotab) showed the best results and thus; they were selected for in-vivo studies in rabbits in comparison with the commercially-available oral tablets; Motinorm®. The selected formulae showed marked enhancement of DMP bioavailability compared with the marketed oral tablets, with relative bioavailability values of 432.49 ±10.13% and 409.32 ±11.59 % for S4 and S8, respectively. The results confirmed that sublingual tablets were promising tool for DMP delivery with marked enhancement of bioavailability.

The aim of this study was to improve the bioavailability of water-insoluble, anti-emetic drug; domperidone (DMP) which has a poor oral bioavailability (13-17%) due to its extensive first pass metabolism. Solid dispersions of DMP with pluronic F-68 were prepared at different weight ratios by fusion method and they were tested for their in-vitro dissolution rate to select the best ratio for tablet formulation. Then, the selected solid dispersions were incorporated into sublingual tablets together with different water-soluble excipients. Sublingual tablets were prepared by direct compression technique and they were evaluated for their physical properties and in-vitro dissolution rate. Sublingual tablets formulae S4 (containing fructose and 10% w/w Ac-Di-Sol) and S8 (containing fructose and 10% w/w Explotab) showed the best results and thus; they were selected for in-vivo studies in rabbits in comparison with the commercially-available oral tablets; Motinorm®. The selected formulae showed marked enhancement of DMP bioavailability compared with the marketed oral tablets, with relative bioavailability values of 432.49 ±10.13% and 409.32 ±11.59 % for S4 and S8, respectively. The results confirmed that sublingual tablets were promising tool for DMP delivery with marked enhancement of bioavailability.

The aim of this study was to improve the bioavailability of water-insoluble, anti-emetic drug; domperidone (DMP) which has a poor oral bioavailability (13-17%) due to its extensive first pass metabolism. Solid dispersions of DMP with pluronic F-68 were prepared at different weight ratios by fusion method and they were tested for their in-vitro dissolution rate to select the best ratio for tablet formulation. Then, the selected solid dispersions were incorporated into sublingual tablets together with different water-soluble excipients. Sublingual tablets were prepared by direct compression technique and they were evaluated for their physical properties and in-vitro dissolution rate. Sublingual tablets formulae S4 (containing fructose and 10% w/w Ac-Di-Sol) and S8 (containing fructose and 10% w/w Explotab) showed the best results and thus; they were selected for in-vivo studies in rabbits in comparison with the commercially-available oral tablets; Motinorm®. The selected formulae showed marked enhancement of DMP bioavailability compared with the marketed oral tablets, with relative bioavailability values of 432.49 ±10.13% and 409.32 ±11.59 % for S4 and S8, respectively. The results confirmed that sublingual tablets were promising tool for DMP delivery with marked enhancement of bioavailability.

Current approaches for optogenetic control of transcription do not mimic the activity of endogenous transcription factors, which act at numerous sites in the genome in a complex interplay with other factors. Optogenetic control of dominant negative versions of endogenous transcription factors provides a mechanism for mimicking the natural regulation of gene expression. Here we describe opto-DN-CREB, a blue-light-controlled inhibitor of the transcription factor CREB created by fusing the dominant negative inhibitor A-CREB to photoactive yellow protein (PYP). A light-driven conformational change in PYP prevents coiled-coil formation between A-CREB and CREB, thereby activating CREB. Optogenetic control of CREB function was characterized in vitro, in HEK293T cells, and in neurons where blue light enabled control of expression of the CREB targets NR4A2 and c-Fos. Dominant negative inhibitors exist for numerous transcription factors; linking these to optogenetic domains offers a general approach for spatiotemporal control of native transcriptional events.

Non-ionic surfactant vesicles were prepared using Span-60 and cholesterol in the mass ratios of 1:1, 2:1, 1:2 and 3:1 for transdermal delivery of an anti-inflammatory drug meloxicam (MXM). The drug encapsulation efficiencies and particle size were observed in the range of 32.9–80.7% and 56.5–133.4 nm, respectively. Three different gel bases were also prepared using Poloxamer-407, Chitosan and Carbopol-934 as polymers to study the performance of the in vitro release of the drug. Prepared gels were also converted into niosomal gels. In vitro release characteristics of MXM from different gels were carried out using dialysis membrane in phosphate buffer (pH 7.4). The poloxamer-407 gel or niosomal poloxamer-407 gel showed the superior drug release over the other formulations. The release data were treated with various mathematical models to assess the relevant parameters. The results showed that the release of MXM from the prepared gels and niosomal gels followed Higuchi’s diffusion model. The flux of MXM was found to be independent on the viscosity of the formulations. The anti-inflammatory effects of MXM from different niosomal gel formulations were evaluated using carrageenan-induced rat paw edema method, which showed superiority of niosomal gels over conventional gels.