The influence of size, specific gravity, and head position on the swallowing of solid preparations

AbstractAimTo clarify the influence of size and specific gravity of solid preparations, and the position of healthy volunteers when swallowing, for the purpose of practical use in patient consultation regarding the taking of medicines.Materials and methodsThe paper reports three studies. Volunteers were asked to swallow four different capsules (A, large and heavy; B, large and light; C, small and heavy; D, small and light) in Study 1, two preparations with different positions (upright, horizontal, and chin-down) in Study 2, and two preparations before and after anesthetization of the bilateral lingual and inferior alveolar nerve in Study 3. The oral transit time (OTT) and pharyngeal transit time (PTT) were evaluated with videofluoroscopy.ResultsThe mean OTT became longer in the order of C, D, B, A. The mean PTT showed no statistically significant differences. The swallowing preference of the four preparations ranked by the subjects showed that difference in size but not the difference in specific gravity is a significant factor. In the chin-down position, OTT was shorter for two preparations, compared with the other two positions. The mean OTT for both the A and B preparations was significantly longer after the bilateral lingual and inferior alveolar nerves were anesthetized.ConclusionWhen swallowing solid preparations, a consideration of size and the position will enable ease of swallowing of medicines. This would especially be the case when delivery of the medicines to be taken by the aged suffering from oral hypoesthesia caused by an underlying disease

Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: Evaluation of drug-drug interactions mediated by organic anion transporter 3

Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H-2 receptor antagonists, are widely used among patients with cancer in clinical practice. The aim of the present study was to analyse the potential drug-drug interactions between MTX and gastric antisecretory drugs in high-dose MTX (HD-MTX) therapy. The impact of PPIs on the plasma MTX concentration on 73cycles of HD-MTX therapy was analysed retrospectively in 43 patients. Also investigated was the involvement of OAT3 in PPI-MTX drug interaction in an in vitro study using human OAT3 expressing HEK293 cells. In a retrospective study, patients who received a PPI had significantly higher MTX levels at 48h (0.38 vs. 0.15mol l(-1), respectively, p=0.000018) and 72h (0.13 vs. 0.05mol l(-1), respectively, p=0.0002) compared with patients who did not receive a PPI (but received famotidine). Moreover, in vitro experiments demonstrated that PPIs (esomeprazole, lansoprazole, omeprazole and rabeprazole) inhibited hOAT3-mediated uptake of MTX in a concentration-dependent manner (IC50 values of 0.40-5.5 m), with a rank order of lansoprazole > esomeprazole > rabeprazole > omeprazole. In contrast to PPIs, famotidine showed little inhibitory effect on hOAT3-mediated MTX uptake. These results demonstrated that co-administration of PPI, but not famotidine, could result in a pharmacokinetic interaction that increases the plasma MTX levels, at least in part, via hOAT3 inhibition

A comparison of oral mucositis in allogeneic hematopoietic stem cell transplantation between conventional and reduced-intensity regimens

Goals of work: Severe oral mucositis developed in allogeneic hematopoietic stem cell transplantation (HSCT) accompanies intolerable pain and risk for systemic bacteremia infection. Conventional stem cell transplantation (CST) and reduced-intensity regimens for allogeneic HSCT (RIST) may differently affect the occurrence and severity of oral mucositis. Here, we comparatively examined oral mucositis in patients undergoing CST and that in RIST patients to search for measures to alleviate oral mucositis. Patients and methods: We retrospectively analyzed the data of 130 consecutive patients undergoing HSCT (conventional, 60; RIST, 70). Oral mucositis was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0. We also investigated risk factors for severe oral mucositis in each regimen. Main results: The incidence of oral mucositis was not significantly different between RIST and CST patients. Use of opioid analgesics to control pain due to oral mucositis was significantly less in patients undergoing RIST compared with those receiving CST. The risk factors for severe oral mucositis, determined by univariate and multivariate analyses, were "younger age (<40)" in CST and "longer duration of neutropenia (≥ 14 days)" in RIST. Conclusions: Although the incidences of oral mucositis were almost the same, the need for opioid analgesics and the risk factors for severe oral mucositis differed between CST and RIST patients