Association between pazopanib exposure and safety in Japanese patients with renal cell carcinoma or soft tissue sarcoma.

The safety and effectiveness of pazopanib are related to plasma trough concentrations in renal cell carcinoma (RCC); however, data on pazopanib plasma trough concentrations with soft tissue sarcoma (STS) are limited. This study investigated the relationship between plasma trough concentrations and pazopanib safety in 45 Japanese patients with RCC or STS. Among the 33 patients included, the median pazopanib trough concentration was 37.

Optimal Timing of Intravenous Acetaminophen Administration for Postoperative Analgesia.

Objective: Acetaminophen (APAP) is widely used as an analgesic for postoperative pain relief. However, the pharmacokinetic-pharmacodynamic (PK-PD) properties of intravenous APAP administration remain unclear. We developed a PK-PD model in adult volunteers.

Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice.

In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for transdermal application: 0.4% aqueous solution, pluronic lecithin organogel (PLO gel), hydrophilic cream, and lipophilic cream.

The selective cytotoxicity of silver thiosulfate, a silver complex, on MCF-7 breast cancer cells through ROS-induced cell death.

Background: Silver is a transition metal that is known to be less toxic than platinum. However, only few studies have reported the anticancer effects of some silver complexes and their possibility as an alternative to platinum complex. This study investigated the anticancer effects of the silver thiosulfate complex (STS), [Ag(SO)], consisting of silver and sodium thiosulfate.

Effects of dosing frequency on the clinical efficacy of ampicillin/sulbactam in Japanese elderly patients with pneumonia: A single-center retrospective observational study.

This study sought to investigate whether dosing frequency (the number of doses per day) affects the antimicrobial efficacy and safety of ampicillin/sulbactam (ABPC/SBT) in Japanese elderly pneumonia patients treated with ABPC/SBT at 6 g/day. This was a retrospective observational study that included hospitalized elderly patients (aged ≥75 years, 10 ml/min ≤CLcr <50 ml/min) who received 3 g every 12 h (BID; n = 61) or 1.5 g every 6 h (QID; n = 45) for the treatment of pneumonia.

Nonlinear Disposition and Metabolic Interactions of Cannabidiol Through CYP3A Inhibition in Rats.

Cannabidiol (CBD) is known to affect the pharmacokinetics of other drugs through metabolic inhibition of CYP2C19 and CYP3A4. However, there is a lack of evidence for such drug interactions. Therefore, we investigated the saturability of CBD metabolism and CBD-drug interactions through inhibition of CYP3A .

[Rubric Assessment for Pharmacotherapy in Spiral Curriculum: Development and Usefulness Evaluation].

A requirement, which students must satisfy, for a diploma at the Showa University School of Pharmacy is the ability to "plan, practice, and assess pharmacotherapy". To continuously assess the ability of students to meet this requirement and to provide patients with proper pharmacotherapy during student clinical rotations, we formulated the "Rubric assessment for pharmacotherapy" and evaluated its usefulness in tutorial learning classes. Clinical pharmacy faculty members created the rubric based on the Subjective, Objective, Assessment, and Plan (SOAP) note guidelines of the university.

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma.

Background/aim: Immune-related adverse events (irAEs) are associated with the efficacy of immune-checkpoint inhibitors in patients with melanoma and non-small cell lung cancer. We therefore evaluated the relationship between irAEs and nivolumab efficacy against metastatic renal cell carcinoma.

Patients And Methods: The medical records of 53 consecutive patients were reviewed and analyzed.

Association of Immune-Related Adverse Events with Pembrolizumab Efficacy in the Treatment of Advanced Urothelial Carcinoma.

Purpose: Immune-related adverse events (irAEs) have been associated with the efficacy of programmed cell death protein 1 (PD-1) inhibitors in patients with urothelial cancer. We therefore evaluated the relationship between irAEs and pembrolizumab efficacy in urothelial cancer patients.

Methods: Patients with urothelial cancer who were treated with pembrolizumab in a second-line setting or later between January 2018 and December 2018 were identified by reviewing their medical records from the Cancer Institute Hospital, Japanese Foundation for Cancer Research.

Development of a Novel Nano-emulsion Formulation to Improve Intestinal Absorption of Cannabidiol.

Background: Cannabidiol (CBD) is highly lipophilic, and its oral bioavailability is known to be very low in humans. In this study, we developed a novel nanoemulsion preparation of CBD (CBD-NE) to improve the poor solubility and absorption of CBD. The pharmacokinetic profiles of CBD in rats were evaluated after oral administrations of CBD oil and CBD-NE, and the effect of bile secretion on CBD absorption was also evaluated.

Association of Hand-Foot Skin Reaction with Regorafenib Efficacy in the Treatment of Metastatic Colorectal Cancer.

Purpose: Hand-foot skin reaction (HFSR) can deteriorate quality of life in patients receiving regorafenib. Cutaneous toxicity is a main adverse effect of multikinase inhibitors and has also been associated with clinical outcome. This study assessed the association between the antitumor efficacy of regorafenib and HFSR in patients with metastatic colorectal cancer (mCRC).

Comparison of adverse events following injection of original or generic docetaxel for the treatment of breast cancer.

Purpose: The approval of injectable generic drugs does not require bioequivalence testing. However, although generic products contain the same level of the active compound, the levels and types of additives present can differ from those used in the original product. Since docetaxel is highly lipophilic, polysorbate 80 (PS80), polyethylene glycol (PEG), and ethyl alcohol are employed to solubilize this anticancer agent.

Hypoglycemic and Antioxidant Activities of the Water Extract of Aquilaria crassna Leaves in Streptozotocin-Nicotinamide-Induced Type-2 Diabetic Mice.

Antidiabetic effect of the water extract of Aquilaria crassna (A. crassna) leaves was recently claimed by some diabetic patients in Thailand, whereas its experimental evidence has not been published yet. The present study was therefore conducted to investigate pharmacological activities of the water extract of A.

Simultaneous optimization of limited sampling points for pharmacokinetic analysis of amrubicin and amrubicinol in cancer patients.

Aim: Limited sampling points for both amrubicin (AMR) and its active metabolite amrubicinol (AMR-OH) were simultaneously optimized using Akaike's information criterion (AIC) calculated by pharmacokinetic modeling.

Methods: In this pharmacokinetic study, 40 mg/m(2) of AMR was administered as a 5-min infusion on three consecutive days to 21 Japanese lung cancer patients. Blood samples were taken at 0, 0.

Synthesis of ¹³C-lidocaine as a probe of breath test for the evaluation of cytochrome P450 activity.

(13)C-Labeled lidocaine, 2-di[1-(13)C]ethylamino-N-(2,6-dimethylphenyl)acetamide (1), was synthesized from [1-(13)C]acetic acid in six steps, as a probe for a breath test to evaluate in vivo cytochrome P450 activity. The measurement of (13)CO2 in breath was successfully performed following oral administration of (13)C-lidocaine 1 to mice.

Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer.

Purpose: The pharmacokinetic (PK)-pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amrubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far. This study was performed to analyze the full PK profiles of amrubicin and amrubicinol and to evaluate their toxicity-PK relationships in Japanese patients.

Methods: Amrubicin (35-40 mg/m(2)) was administered to 21 lung cancer patients on days 1-3 every 3-4 weeks.

The use of 13C-erythromycin as an in vivo probe to evaluate CYP3A-mediated drug interactions in rats.

(14)C-erythromycin breath test has been utilized to evaluate the extent of CYP3A activity in vivo. However, its radioactivity sometimes impedes its clinical application. In this study, we employed erythromycin labeled with (13)C ((13)C-EM), a nonradioactive stable isotope, as an in vivo probe of breath test to evaluate CYP3A-mediated drug interactions in rats.

Estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, based on physiological liver development and serum protein levels.

We established a method for estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, using the free fraction of drug in plasma (fu), serum protein level (P), liver volume (LV), and CYP activity (Vmax/Km) as indices of physiological and biochemical development in children up to 15 years old. This method allows the child/adult dose ratio (D(C)/D(A))=child/adult oral clearance ratio (CL((PO)(C))/CL((PO)(A))) of drugs mainly metabolized in the liver to be estimated by the following equation: [formula: see text]. Major metabolism of drugs was ascribed to CYP1A2 for theophylline and caffeine, and CYP1A2 and CYP2D6 for propranolol and mexiletine.

Comparison of physicians' compliance, clinical efficacy, and drug cost before and after introduction of Asthma Prevention and Management Guidelines in Japan (JGL2003).

Background: This study investigated the variations in the clinical efficacy and drug cost following the introduction of the Asthma Prevention and Management Guidelines in Japan (JGL2003).

Methods: The medical charts of fifty outpatients treated continuously for asthma, aged 16-50 years, from October 2002 to October 2004 at Showa University Hospital were analyzed for physicians' compliance with asthma guidelines, symptom severity, episodes in various occasions, prescriptions and drug costs.

Results: Physicians' compliance with the guidelines, which were defined as the number of patient visits treated in conformity with the JGL over the total number of patient visits, was found to be high before (89.

Desirable pharmacokinetic properties of (13)C-uracil as a breath test probe of gastric emptying in comparison with (13)C-acetate and (13)C-octanoate in rats.

Objective: To investigate the possible use of a (13)C-uracil breath test for gastric emptying by evaluating the pharmacokinetic properties of (13)C-uracil in a breath test in rats, in comparison with (13)C-acetate and (13)C-octanoate, traditional (13)C-probes for gastric emptying.

Material And Methods: Absorption of the (13)C-probes from different parts of the gastrointestinal tract was evaluated in fasted rats. (13)C-Uracil breath tests for gastric emptying were carried out in conditions where delayed gastric emptying was induced by clonidine, quinpirole, and propantheline, and in a postoperative ileus model.

[Dose estimation for renal-excretion drugs in neonates and infants based on physiological development of renal function].

We established dose estimation formulae for renal-excretion drugs using the glomerular filtration rate (GFR), tubular secretion clearance (Sc), and unbound fraction of drug in plasma (fp) as a renal function index of physiological development in neonates and infants not more than 2 years of age. A dose ratio of (DC/DA)=clearance ratio of (CLC/CLA) congruent with(fpC.GFRC)/(fpA.

Ethyl docosahexaenoate decreased Neoral absorption due to particle size enlargement.

We recently reported that docosahexaenoic acid (DHA) enhanced the bioavailability of cyclosporine A (CsA) in a conventional oil formulation by inhibiting CYP3A-mediated gut metabolism. The aim of this study was to evaluate the effect of ethyl docosahexaenoate (DHA-EE), the commercially available form of DHA, on the absorption of CsA from its microemulsion formulation, Neoral, in rats. AUC(infinity), AUC(0-10h) and C(max) of CsA decreased significantly when DHA-EE was co-administered, indicating that CsA absorption was diminished by DHA-EE.

Pharmacokinetic and pharmacodynamic analyses, based on dopamine D2-receptor occupancy of bromocriptine, of bromocriptine-induced contralateral rotations in unilaterally 6-OHDA-lesioned rats.

Bromocriptine is a selective agonist for dopamine D2-receptors and is used in the treatment of Parkinson's disease. In this study, we performed pharmacokinetic and pharmacodynamic (PK/PD) analyses of the antiparkinsonian effect of bromocriptine and evaluated drug-induced contralateral rotations in rats in which unilateral striatal lesions had been generated by microinjection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The plasma concentration (Cp) and D2 receptor occupancy (Phi(D2)) were quantitated by HPLC and with an in vivo back-titration method using [(3)H]-raclopride, respectively.

A new method for determination of buformin in plasma and urine by ion-paired reversed-phase HPLC with ultraviolet detection.

Buformin is a widely used as an antidiabetic agent but its renal excretion is still controversial. A new HPLC method with ultraviolet (UV) detection for the determination of buformin in plasma and urine has been developed. After protein precipitation or dilution, buformin and internal standard phenformin were resolved on an octadecyl silica column and detected by UV detection at 233 nm.