Receptor occupancy is an indicator of antipsychotic efficacy and safety. It is desirable to simultaneously determine the occupancy of multiple brain receptors as an indicator of the efficacy and central side effects of antipsychotics because many of these drugs have binding affinities for various receptors, such as dopamine 2 (D), histamine 1 (H), and muscarinic acetylcholine (mACh) receptors. The purpose of this study was to develop a method for the simultaneous measurement of multiple receptor occupancies in the brain by the simultaneous quantification of unlabeled tracer levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
View Article and Find Full Text PDFLactononadecapeptide (LNDP; NIPPLTQTPVVVPPFLQPE), a casein-derived peptide comprising 19 residues, is known for its capacity to enhance cognitive function. This study aimed to explore the transepithelial transport and stability of LNDP. Results showed that LNDP retained over 90% stability after 2 h of treatment with gastrointestinal enzymes.
View Article and Find Full Text PDFObjective: Visual analog scale (VAS) can be used to evaluate multiple parameters. There have been no reports on the verification of order effects or reproducibility of the VAS method for overall palatability of oral dosage forms. The purpose of this study was to assess the validity of a method for evaluating the palatability of orally disintegrating tablets (ODTs) using a 100-mm VAS.
View Article and Find Full Text PDFTo assess the pharmacologically relevant and selective muscarinic receptor occupancy in the bladder mucosa, we considered not only plasma drug concentrations but also urinary drug concentrations. The purpose of this study was to predict muscarinic receptor occupancy in the human bladder mucosa based on urinary concentrations in response to clinical dosages of antimuscarinic agents used to treat overactive bladder. The calculated mean plasma or serum unbound steady state concentrations were 0.
View Article and Find Full Text PDFWe report on the development of an on-site therapeutic drug monitoring (TDM) method for vancomycin (VCM) utilizing a portable spectrometer and commercially available immunoturbidimetric assay reagents designed for automated clinical chemistry analyzers. The method enables the quantification of VCM in plasma samples within 10 min, with a good correlation between the measured values and the theoretical values (r = 0.995).
View Article and Find Full Text PDFGood adherence to medication is critical for successfully treating psychiatric disorders. Tailor-made pharmaceutical formulations can provide a suitable dosage form to meet the specific needs of individual patients who exhibit poor adherence to industrially manufactured products. Herein, we prepared aripiprazole (ARP) gummies (ARP-Gs) using a commercially available ARP formulation.
View Article and Find Full Text PDFThis study aimed to elucidate the characteristics and pharmacokinetics of orally disintegrating tablets (ODTs) containing coenzyme Q10 (CoQ10) granules prepared by spray drying, hot-melting, and wet granulation. The hardness and disintegration times of CoQ10-ODTs containing 5 % crospovidone were 61.6-81.
View Article and Find Full Text PDFChem Pharm Bull (Tokyo)
October 2021
The aim of the present study was to determine whether solid dispersions (SDs) are applicable to gummi formulations. Amenamevir was selected as a model of a poorly water-soluble drug, and polyvinyl alcohols (PVAs) with various degrees of hydrolysis (PVA 66, PVA 80, PVA 88, and PVA 66/88) were used as SD carriers. Design of experiments (DOE) was used to develop a gummi formulation that was suitable for an amenamevir SD using SD with PVA 66.
View Article and Find Full Text PDFA cocktail study is an in vivo evaluation method to assess multiple CYP activities via a single trial and single administration of a cocktail drug that is a combination of multiple CYP substrates. However, multiple blood samples are required to evaluate the pharmacokinetics of a CYP probe drug. A limited-point sampling method is generally beneficial in clinical studies because of the simplified protocol and reduced participant burden.
View Article and Find Full Text PDFOral mucositis is one of the most common adverse effects of radiation and chemotherapy in treatments of cancers. Some clinical guidelines have focused on the prevention and treatment of oral mucositis, and thus, a mouthwash containing drugs is often recommended. In this study, we aimed to evaluate the disappearance time and palatability in the oral cavities of healthy volunteers in foams prepared from different concentrations of the three viscosity grades of methylcellulose (SM-4, -100, -400).
View Article and Find Full Text PDFA cocktail approach is a method to comprehensively evaluate the activity of cytochrome P450 enzymes (CYPs) by co-administering multiple CYP substrates. This is the first report that compares the results from a cocktail study to a single substrate separate administration study (single study) with concomitant administration of CYP inducers/inhibitors. The validity of a cocktail study for use as a quantitative drug-drug interactions (DDIs) assessment was evaluated.
View Article and Find Full Text PDFThe taste of medicines can significantly affect patient adherence. Pediatric patients often cannot take powder medicines because of their unpleasant taste. Therefore, patients' parents and health care professionals, including pharmacists, often combine medicines with food or beverages to make them easier for pediatric patients to consume because this can reduce their unpleasant taste.
View Article and Find Full Text PDFRaman analysis has higher sensitivity for the detection of active pharmaceutical ingredients (APIs) than additives; thus, it is expected to be used for the evaluation of low-content preparations. The purpose of this study was to clarify the usefulness of granule morphology assessment using Raman analysis in the development of low-content formulations. In this study, midazolam was used as a model drug to prepare granules as a low-content formulation.
View Article and Find Full Text PDFRecently, owing to their pharmaceutical and clinical utility, mini-tablets have been well studied by researchers. Mini-tablets are usually manufactured by compression molding using a multiple-tip tool in a rotary tableting machine. Owing to their special structure, ensuring uniformity is a very important challenge in the manufacturability of mini-tablets using the multiple-tip tool.
View Article and Find Full Text PDFAims: The strong cytochrome P450 (CYP) 2C8 inhibitor gemfibrozil has been demonstrated to increase the area under the plasma concentration-time curve from 0 to infinity (AUC ) of ACT-333679, an active metabolite of selexipag, by 11-fold. Similarly to gemfibrozil, the CYP2C8 inhibitor clopidogrel increased ACT-333679 concentration by 1.9-fold after a single loading dose (300 mg once daily) and 2.
View Article and Find Full Text PDFBackground Administration of phosphate binders can decrease serum phosphate levels and improve the prognosis of patients on dialysis. However, patients are often non-adherent to phosphate binder medication. Although community pharmacist-led education could be effective in the maintenance of adherence to phosphate binder medication, its impact has not been evaluated.
View Article and Find Full Text PDFInt J Clin Pharmacol Ther
November 2020
Aims: Opioids are commonly used analgesics for moderate to severe pain, but levels of drug effect vary among individuals. As for the mechanisms underlying these individual differences, there have been reports suggesting effects of polymorphisms in the gene encoding μ-opioid receptor (). However, whether these polymorphisms affect the actions of μ-opioid receptor partial agonists has yet to be determined.
View Article and Find Full Text PDFIntroduction: With an increase in the incidence of Staphylococcus aureus infections in the healthcare settings and in the community, trimethoprim/sulfamethoxazole (TMP/SMX) has been suggested as a convenient treatment option. However, the appropriate dosage regimen of TMP/SMX is unclear.
Objective: This study aimed to examine the pharmacokinetics/pharmacodynamics (PK/PD) of TMP/SMX against S.
Chem Pharm Bull (Tokyo)
January 2020
Solifenacin (Sol), an antimuscarinic agent has been widely used for the treatment of overactive bladder. Transdermal formulations can be administered without water as well as absorbed slowly into the blood over a long period of time. The aim of this study was to develop cream and tape formulations of Sol, and evaluate the transdermal permeation and absorption of the drug from the two formulations in vitro and in vivo, respectively.
View Article and Find Full Text PDFBackground: The prevalence of pulmonary infections caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Furthermore, the treatment of infections caused by the complex (MAC) remains challenging. The cytochrome P450 (CYP) enzyme inducer, rifampicin, and the CYP inhibitor, clarithromycin, have clinical activity against MAC and key drugs in the treatment of MAC infection.
View Article and Find Full Text PDFThere are large inter- and intra-individual variations in CYP3A4 activity. Midazolam, which is predominantly metabolized to 1'-hydroxymidazolam and 4-hydroxymidazolam by CYP3A4, is considered an effective probe for CYP3A4. To determine the area under the curve (AUC) of midazolam or midazolam clearance for CYP3A4 activity, multiple plasma samples of midazolam are required.
View Article and Find Full Text PDFFixed-dose combination (FDC) medicines containing two or more active pharmaceutical ingredients (APIs) in a single dosage form have been reported to improve patient adherence to a greater extent than single dosages of individual components (ICs). Orally disintegrating tablets (ODTs) are easier to swallow than conventional tablets. The aim of this study was to elucidate the clinical pharmaceutical characteristics of taking a FDC-ODT and two IC-ODTs.
View Article and Find Full Text PDFPolymorphisms of cytochrome P450 (CYP) enzymes can affect enzymatic activity, drug metabolism and drug interactions. Although the potential for drug interactions is especially important when co-administering drugs with strong inductive or inhibitory potential towards drug-metabolizing enzymes, the relationship between CYP genotypes and the extent of the inductive or inhibitory effects remain poorly understood. We investigated the effects of rifampicin (inductive) and fluvoxamine (inhibitory) on metabolism of omeprazole and CYP2C19 enzymatic activity in 19 healthy Japanese subjects.
View Article and Find Full Text PDF