Effect of Thickening Agents on the In Vitro Antibacterial Activity of Vancomycin Hydrochloride Powder.

When vancomycin hydrochloride (VCM) powder mixes with xanthan gum-based thickening agents in food, lumps or other property-related changes may occur. Previous studies have reported delayed disintegration and elution of the drug and its adsorption on to xanthan gum, which is the main ingredient of thickened food products. If the addition of thickening agents can affect the antimicrobial activity of VCM powder as previously reported, it might interfere with the treatment of Clostridioides difficile infection (CDI). In this study, we investigated the effect of the addition of xanthan gum-based thickening agents on the antibacterial activity of VCM against Clostridioides difficile in vitro. The VCM concentration at 0 min after adding 3% Tsururinko Quickly (Clinico, Tokyo) to VCM powders (Shionogi, Osaka and Meiji Seika Pharma, Tokyo) was lower than that of the control [Shionogi: 65.15±35.57%, Meiji Seika Pharma: 77.00±15.81% (mean±standard deviation), ** p<0.01, Dunnet's test]. However, the VCM concentration at 30 min after the addition recovered to the control level. The drug susceptibility tests for C. difficile and Staphylococcus aureus using the disk diffusion method showed no effect of addition of 3% Tsururinko Quickly. Our in vitro evaluations showed that the addition of xanthan gum-based thickeners to VCM powders had a negligible effect on the treatment of CDI.

Optimal Administration of Phosphorus Adsorbents When Using Medical Nutritional Supplements for Tube-fed Patients.

All medical enteral nutrition products contain phosphorus and when administered to patients with chronic kidney disease (CKD) and on dialysis, they lead to the risk of elevated serum phosphorus levels. Thus, serum phosphorus levels should be monitored, and phosphorus adsorbents should be used in cases of high serum phosphorus levels. In this study, we investigated the effect of phosphorus adsorbents on enteral nutrition, using Ensure Liquid®, a medical nutritional formula, for patients with CKD and those on dialysis. Additionally, we compared the effects of the simple suspension method, in which various phosphorus-adsorbing agents are suspended and mixed directly with the nutritional formula for tube administration (hereafter referred to as the "pre-mix method"), and the conventional method, in which only the phosphorus-adsorbing agents are administered separately from the nutritional formula for tube administration (hereafter referred to as the "normal administration method"). The administration of various phosphorus adsorbents using the pre-mix technique resulted in a phosphorus removal rate of 8-15% (approximately 12% on average). Therefore, through the pre-mix method, maintaining the phosphorus content of Ensure Liquid® below the daily phosphorus intake standard was possible for patients on dialysis. The pre-mix method via the simple suspension method of administering phosphorus adsorbent with Ensure Liquid® resulted in less drug adsorption to the injector and tube and a higher phosphorus removal rate than the normal administration method.

[Comparison of the Pharmaceutical Characteristics of Brand-name and Generic Pramipexole Extended-release Tablets and Their PTP Usability].

The pramipexole extended-release (long acting) tablet, a D2 receptor agonist commonly used for the treatment of Parkinson's disease, has increasingly demonstrated usability for patients with long acting performance and patient adherence improvements. As a generic drug it is sold by six companies while a brand name drug is also marketed. As these formulations are hygroscopic it is described as such in package inserts so that tablets will only be removed from the press-through package (PTP) immediately before ingestion. It is often dispensed in one-dose packaging (ODP) as determined by a patient's physical functions and symptom characteristics. With ODP, quality control and ease of removal from the PTP are important factors. In this study we examined the stability of tablets in the ODP (25℃ RH75%) while also comparing the ease of handling of the seven products currently marketed in Japan. In the tablets' ODP, changes such as swelling and decreases in tablets hardness were observed in six formulations. Differences were found among the products in comparison of packaging material, required tablet extrusion strength, and ease of removal. Given the differences in PTP materials and hygroscopicity it is suggested that pharmacists must not only consider the drug formulations of products but also contribute to improvements in medication adherence for patients with poor hand-finger function.

Increases in bioavailability of poorly absorbed drug by acylcarnitine.

We examined the effect of acylcarnitines on the in situ bioavailability of lucifer yellow (LY) from the loops of small and large intestines of rats. The area under the blood concentration of LY versus time curve (AUC) from the jejunum was significantly increased by the treatments of the loop with 100 µM lauroylcarnitine (LC) or 100 µM palmitoylcarnitine (PC) (fourfold and 17-fold, respectively). No marked change in the expression of claudin-4 protein was observed by the treatments. On the contrary, the expression of P-glycoprotein (P-gp) was decreased by the treatment, more greatly by PC than by LC, suggesting that increases in the bioavailability of LY by LC and PC are associated with the decreased expression of P-gp in jejunum. The increase in the bioavailability was also observed for colon by the treatment of LC, but not that of PC. LC decreased the expression of claudin-4 protein, whereas PC decreased the expression of P-gp in colon. Therefore, LC and PC appear to have different impact on the intestinal transporters depending on the site (i.e., jejunum and colon).

Absorption enhancement effect of acylcarnitines through changes in tight junction protein in Caco-2 cell monolayers.

We investigated the effects of lauroylcarnitine and palmitoylcarnitine on major tight junction proteins such as claudins in Caco-2 cell monolayers and also examined the involvement of cholesterol in the effects induced by both acylcarnitines on these proteins. We investigated the effects of lauroylcarnitine and palmitoylcarnitine on the barrier function of tight junctions by measuring transepithelial electrical resistance (TEER) and fluorescein isothiocyanate dextran 40,000 (FD-40) flux. A decrease in the TEER value and an increase in FD-40 flux were observed after incubating Caco-2 cell monolayers with lauroylcarnitine and palmitoylcarnitine for 1 h, suggesting the loss of the barrier function of tight junctions. In addition, lauroylcarnitine and palmitoylcarnitine decreased the protein levels of claudin 1, 4, and 5 but not those of claudin 2, 3, 6, or 7. In addition, palmitoylcarnitine and methyl-ß-cyclodextrin increased cholesterol release from the plasma membrane. It is suggested that the effects of palmitoylcarnitine and methyl-ß-cyclodextrin on claudin 4 and 5 may be associated with cholesterol leakage from the plasma membrane into the apical side. These results indicate that the protein levels of claudin 4 and 5 are decreased by treatment with palmitoylcarnitine and lauroylcarnitine, and that this change is involved in the absorption-enhancing mechanism.

Effects of acylcarnitines on efflux transporting system in Caco-2 cell monolayers.

This study examined the effects of the absorption enhancers, acylcarnitines, on efflux transporting systems, including P-glycoprotein (P-gp) and other efflux transporters, and elucidated the importance of acyl chain length and the concentration of acylcarnitine on the activity of efflux transport. The effects of two acyl (lauroyl and palmitoyl) carnitines on the influx and efflux of lucifer yellow and fluorescein isothiocyanate dextran 4,000, which have characteristic vectorial transport, were examined in Caco-2 cell monolayers. Lauroylcarnitine and palmitoylcarnitine increased influx and decreased efflux of these substrates, in a manner dependent on their concentration and acyl chain lengths by increasing influx and inhibiting efflux of the substrates. The results indicated that both the acyl moiety and long acyl chains play important roles in the modification of influx and efflux transport. Because no marked changes in the levels of P-gp protein or the leakage of LDH were observed at 1 h after the application of acylcarnitines, it was concluded that these acylcarnitines had an effect on modulation of the function of P-gp or other efflux transporters without cytotoxicity.