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We propose the name of the subject of pharmacology education/learning for midwives as "Midwifery Pharmacology" and the basic education/learning items. The content will consist of "General Introduction (Anatomy and Physiology, Pharmaceutics, Pharmacokinetics, and Clinical Laboratory Medicine)", "Pharmacodynamics" and "Clinical Pharmacology". The common theme of all these contents is the relationship with pharmaceuticals from pregnancy to childbirth and lactation. In the general introduction, anatomical and physiological changes, pharmacokinetic changes, and clinical laboratory medicine in the mother and child during pregnancy are covered. In pharmacodynamics, students learn about the effects, mechanism of action, side effects, and interactions of drugs during pregnancy. Clinical pharmacology deal with drugs used from pregnancy to delivery, and diseases that are likely to oocur during pregnancy and delivery. In addition, the content includes items on questions and concerns of patients and their surroundings, counseling, and collection of information. Based on the content of each of the above items, the selection of diseases and medicines, and the severity and depth of the items are selected and added independently by each field or area, and adjusted in consideration of time, number of credits. [ABSTRACT FROM AUTHOR]

Among the four pharmacological component subjects: "pharmaceuticsH, npharmacokineticsn, "pharmacodynamics", and "clinical pharmacology (pharmacotherapy, applied pharmacology)H, in clinical pharmacology targeting diseases and applicable drugs, drugs/diseases are selected as "drugs from diseases" instead of "diseases from drugs" based on the following four taxonomies. Clinical pharmacology consists of diseases and applicable drugs classified and selected by either clinical departments, organs, symptoms, or specialized education subjects, or by their combination. The other three subjects of pharmaceutics, pharmacokinetics, and pharmacodynamics are created by combining drugs for explain the basic contents of each subject and diseases/drugs classified and selected in clinical pharmacology. Pharmacology component subjects are learned in the following order: "pharmaceutics", "pharmacokinetics'1, "pharmacodynamics", and "clinical pharmacology (pharmacotherapy, applied pharmacology)M. In order to increase the effectiveness of these learnings, it is essential to have books on the four phannacological component subjects constructed by these methods. [ABSTRACT FROM AUTHOR]

It is proposed that the four subjects: "Pharmaceutics", "Pharmacokinetics", "Pharmacodynamics" and "Clinical Pharmacology (Applied Pharmacology, Pharmacotherapeutics etc.)" in the curriculum of pharmacology education in all medical fields are disciplined, and that time and credits be allocated separately. Pharmacology practice should be conducted by combining animal and simulation practice. For the education of pharmacology in the co-medical field, there is an urgent need to train teachers who have a background in each field and a research mindset in pharmacology. By introducing these four subjects, students will be able to obtain stable knowledge and understanding of pharmacology in each field. As a result, a large number of high quality medical professionals with knowledge and skills based on scientific evidence and a research mindset will be produced in each field. Above all, we hope that advanced medical care will be provided to patients in the medical field through better medical cooperation. [ABSTRACT FROM AUTHOR]

Patients with special backgrounds such as organ dysfunction, elderly individuals, children, and pregnant or nursing women in whom the pharmacokinetics of an agent are expected to differ from those observed in the general patient population, are referred to as "special populations." Administration of drug therapy to these patients warrants close attention to and knowledge of altered pharmacokinetics to design appropriate personalized dosing regimens. In this study, we investigated the effects of hypothermia and renal impairment on drug pharmacokinetics, focusing on tissue distribution. Analysis of the effects of hypothermia on local liver kinetics of drugs revealed decreased activity of drug-metabolizing enzymes and transporters. Furthermore, we investigated in vivo drug pharmacokinetics and observed that blood drug concentrations increased with a decrease in the body temperature. However, the tissue concentration of midazolam (MDZ) remained unchanged even with a decrease in body temperature, which indicates reduced tissue transfer of MDZ. With regard to the effect of renal impairment, blood concentration of MDZ decreased in patients with acute renal failure and increased in those with chronic renal failure. However, MDZ clearance was decreased in patients with chronic renal failure owing to decreased expression of hepatic metabolic enzymes and reduced hepatic blood flow. This study highlights that tissue translocation of drugs differs across special populations and that optimization of drug administration based on the prediction of tissue concentrations is important.

The pharmacokinetic (PK)/pharmacodynamic (PD) approach has been widely used in clinical practice to optimize antimicrobial treatment. To promote the appropriate use of antimicrobial agents, it is important to consider certain factors, such as patient (e.g., age, physique, medical history, comorbidities, and organ dysfunction), site of infection (the target site where many causative bacteria are present), and microorganism (causative bacteria and susceptibility), and the dosing regimen should be selected based on the PK/PD approach. However, for renally excreted antibiotics, dosing regimens based on only renal function, such as creatinine clearance, are mainly used. Therefore, other factors such as patient pathological factors, antibiotic penetration of target sites, susceptibility of the causative bacteria to antibiotic, and clinical evaluation (efficacy and toxicity) should be considered simultaneously. These studies aimed to tailor the dosing of antimicrobial agents to individual patients by considering these factors. Multifaceted PK/PD evaluation may improve antimicrobial efficacy and safety, thereby contributing to the successful treatment of infectious diseases. Furthermore, improved treatment success rates may help manage the prevalence of antimicrobial-resistant bacteria, which is expected to become a significant problem in the future.

Drug therapy during pregnancy and lactation is determined by a balance of risks and benefits. Successful control of disease during pregnancy is necessary for a favorable pregnancy outcome. This lecture will focus on basic concepts.

The Faculty of Pharmaceutical Sciences, Kobe Gakuin University has collaborated in clinical research with Kobe City Medical Center General Hospital. In this university-medical institution collaboration, university faculty members discuss clinical problems with on-site pharmacists and doctors, and carry out clinical research to resolve these problems. During the coronavirus disease 2019 (COVID-19) pandemic, many patients with COVID-19 were treated at Kobe City Medical Center General Hospital. In February 2020, during the first increase in the number of patients with COVID-19 in Japan, treatment for COVID-19 was not established, and some existing anti-viral drugs, such as favipiravir, were experimentally used for COVID-19 treatment. However, since these drugs were not developed specifically for treating COVID-19, their pharmacokinetics have not been sufficiently studied. In particular, the pharmacokinetics of favipiravir in critically ill patients with COVID-19 was of concern, because critically ill patients have an urgent need for life-saving anti-viral drug treatment. Therefore, we conducted a collaborative clinical study to evaluate the pharmacokinetics of favipiravir in patients with COVID-19. The blood concentration of favipiravir in patients with COVID-19 at Kobe City Medical Center General Hospital was measured by lipid chromatography-tandem mass spectrometry at Kobe Gakuin University. Population pharmacokinetics analysis was then performed. In this symposium review, we introduce our pharmacokinetic study of antiviral drugs in patients with COVID-19, focusing on the university-medical institution collaboration. We believe collaborative clinical research will be useful for solving clinical issues and ensuring the effectiveness and safety of pharmacotherapies.

The evaluation and prediction of pharmacokinetics in humans is important in the field of drug discovery and development. Generally, human pharmacokinetics is predicted using physiologically based pharmacokinetic models that include physiological and physicochemical (drug) parameters obtained from in vitro assays. Specific organ dysfunction, such as liver disease, also affects the functions of other organs, causing unexpected pharmacokinetic fluctuations. I investigated the effect of cholestasis on intestinal drug absorption in mice subjected to bile duct ligation (BDL). The intestinal absorption and permeability of imatinib was decreased in BDL mice compared with sham-operated mice, and this may be attributed to the up-regulation of the efflux transporter, breast cancer resistance protein. However, a single-organ experimental system cannot predict such pharmacokinetic changes. To overcome this challenge, I investigated a microphysiological system (MPS) equipped with intestinal and hepatic cells for pharmacokinetic evaluation. The glucuronidation of triazolam was significantly increased in an enterohepatic MPS compared with a single-culture system. These results suggested that the elucidation of organ interactions requires the use of an MPS loaded with human cells in combination with laboratory animal studies. In this review, I present the results of my evaluation of organ interactions using animal models and MPSs in the Award for Young Scientists from the Pharmaceutical Society of Japan, Hokuriku Branch.

Sinomenine (SIN) is a major component contained in extracts of the Chinese medicinal herb Sinomenium acutum. SIN has various pharmacological properties, including cytoprotection, immunosuppression and anti-inflammation effects. Furthermore, recent studies have reported that SIN has anti-tumor and antidepressant effects, which has created a strong need for SIN kinetic studies. This paper reports a simple and sensitive competitive enzyme-linked immunosorbent assay (ELISA) for the pharmacokinetic evaluation of SIN. Anti-SIN serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and carboxylic modified SIN using the N-succinimidyl ester method. Enzyme labeling of SIN with horseradish peroxidase was similarly performed using carboxylic modified SIN. Under optimized conditions, this ELISA shows a linear detection range from 40 to 5000 pg/mL, and a limit of detection of 12.1 pg/mL for 50-µL samples. This assay was specific for SIN and showed very slight cross-reactivity with dextromethorphan (0.45%), dimemorfan (0.22%) and codeine (0.01%), but no cross-reactivity with 2-methoxycyclohex-2-enone (<0.001%). Using this ELISA, SIN levels were easily determined in the blood of mice after oral administration of Kampo medicine, Boiogito. The ELISA may be a valuable tool for studies of the biological and pharmacological properties of SIN.

ATP-binding cassette (ABC) transporters, which comprise the largest gene-family in humans, are membrane proteins that transport various substrates, depending on ATP hydrolysis. Among these transporters, several include ABCB1 (P-glycoprotein), identified here for the first time in humans, which exports anti-cancer drugs from cancer cells, thus participating in multidrug resistance (MDR). ABC transporters also export drugs, in general, from the human body, therefore affecting overall pharmacokinetics. We have contributed, here, to a better understanding of the role of these exporter proteins in two aspects. First, we have cloned the human ABCC2 gene and identified mutations in hereditary hyperbilirubinemia patients, demonstrating the role of ABCC2 as a xenobiotic export pump. Second, we also found an unexpected role of ABCB1 in cancer, in that it promotes tumor initiation independently of the MDR phenomenon, which was further confirmed by a chemoprevention experiment using verapamil, an ABCB1 inhibitor. In this review, I discuss the role of ABC transporters, both in biodefense against xenobiotics and in cancer development and malignant alterations, based on our results as well as the studies of others.

Vancomycin is the first-choice antimicrobial for the lethal methicillin-resistant Staphylococcus aureus infections. Therefore, the therapeutic performance of vancomycin must be enhanced. The narrow therapeutic range between clinical efficacy and toxicity necessitates therapeutic drug monitoring. Therapeutic targets were previously established by trough concentrations (10-20 μg/mL) but are now commonly determined with the area under the concentration-time curves (AUC, 400-600 μg·h/mL). However, there has not been a strategy for efficiently calculating individual AUC. This review focuses on studies pertaining to activating AUC-guided dosing of vancomycin in clinical settings. First, the author suggested a table for determining empirical dosing of vancomycin by population pharmacokinetic analysis, where weight-normalized dosing corresponded to the estimated glomerular filtration rate, also as in the case during continuous renal replacement therapy (CRRT). The author then demonstrated that Bayesian forecasting was effective for CRRT patients in regards to compliance with a target therapeutic range. The author also developed a web application to enable AUC-guided dosing. Finally, the author demonstrated a reduction in patients developing nephrotoxicity following an intervention against the concomitant use of vancomycin and tazobactam/piperacillin, a known risk factor for acute kidney injury.

The nasal drug application has drawn much attention as the strategy for the delivery route of many drug modalities such as the poorly absorbed drugs, peptides, nucleic acid, and central nervous system drugs. The absorption of drug after intranasal (IN) application depends on the nasal residence time of applied drug, affected by mucociliary clearance (MC). MC is a decisive factor in the nasal absorption of drug. We describe the establishment of in vitro evaluation system of nasal MC via the moving velocity of a marker particle on nasal mucosa, and the development of the pharmacokinetic model to which in vitro parameters on nasal MC was incorporated to enable the prediction of drug absorption after IN application. Moreover, the pharmacokinetics of norfloxacin after IN application was investigated using MC-modified rats pretreated with MC modulators. Nasal absorption fluctuated due to changes in the nasal residence time of drug in response to changes in MC. The prediction system enables quantitative evaluation of changes in drug absorption associated with MC fluctuations. In addition, for a precise prediction system for drug absorption after IN application from the drug absorption model, the relationships between in vitro drug permeability through Calu-3 layers, in vivo transnasal permeation of drug and in vivo bioavailability after IN application were evaluated. The significant correlations between these parameters were obtained, suggesting that transnasal permeability and drug absorption after IN application can be predicted from in vitro membrane permeability.

Ascertaining the absorption, distribution, metabolism, and excretion (ADME) profile of drugs is one of the most crucial factors in the process of drug discovery. Since it is important to combine water solubility and cell permeability within the compound to achieve the desired ADME properties, an appropriate balance between lipophilicity and hydrophilicity is required. It is often necessary to facilitate hydrophilicity of very hydrophobic candidates, because quite lipophobic molecules are rarely hit as positive in molecular-targeted or cell-based screenings. For that purpose, it has been popular to conjugate hydrophobic molecules with polyethylene glycol (PEG). However, PEG is a polymer, and PEG-conjugated molecules are not uniform. Besides, the dosage should be much increased compared with the original molecule due to the increase in molecular weight. Therefore we have been developing alternative ways to endow hydrophobic compounds with extra hydrophilicity by conjugating with symmetrically branched glycerol oligomers. This technology is versatile and easily applicable to various hydrophobic compounds. Water-solubility of fenofibrate, one of the most hydrophobic medicines in clinical use, was facilitated by a factor of more than 2000, and its lipid-lowering effect in vivo improved more than ten-fold, by simply conjugating with branched glycerol trimer, for instance. Here we will briefly introduce the basic concepts and our successful experiences of applying branched glycerol oligomers including antitumor agents in terms of water-solubility, pharmacological effects, and pharmacokinetics, and merits and current issues will be discussed in this review.

Daptomycin (DAP) has a completely different mechanism of action compared to conventional methicillin-resistant Staphylococcus aureus (MRSA) drugs and is widely used clinically as the first-line drug for the treatment of skin soft tissue infection and sepsis caused by MRSA infection. However, the most serious side effects of DAP include renal dysfunction and rhabdomyolysis. Knowledge of the time sequence of localization of DAP in cells and tissues of animals may help in developing a better understanding of the actual overall pharmacokinetics of DAP. We prepared DAP-specific antibodies by immunizing mice with DAP-GMBS-BSA conjugate. The Anti-DAP antibody was specific for DAP, which enabled us to develop an immunocytochemical method for detecting the uptake of DAP in the rat kidneys. One hour after a single intravenous (i.v.) injection of DAP at 12 mg/kg, immunohistochemical observation showed a strong ring-like positive reaction in the cytoplasm immediately below the microvilli of proximal tubule epithelial cells. The distal tubules and collecting ducts contained DAP-positive and negative cells in the cross section of one tubule. Twenty-four hours after DAP administration, several strong positive reactions of different sizes were observed in the cytoplasm of epithelial cells at the proximal tubule. No staining was detected after 7 days. This study will be a useful tool for analyzing the pharmacokinetics of DAP.

Modification of proteins with polyethylene glycol (PEG) (PEGylation) is a gold standard technique that improves the solubility, pharmacokinetics, and immunogenicity of modified proteins. To date more than 10 PEGylated protein formulations have been approved, and more than 20 PEGylated drugs are entering clinical trials. PEG has been considered non-immunogenic and non-toxic, but several studies have shown that PEG acquires immunogenicity following attachment to nanoparticles. The administration of PEGylated liposomes, micelles and proteins induces the production of antibodies against PEG (anti-PEG antibodies) in animals and human subjects. Indeed, approximately 20% of healthy human subjects possess pre-existing anti-PEG antibodies prior to treatment with PEGylated therapeutics. The induced and pre-existing anti-PEG antibodies cause not only the elimination of PEGylated proteins from blood circulation, but also allergic responses via the release of anaphylatoxins. Consequently, therapeutic outcomes for PEGylated proteins are impaired. The utility of PEGylated proteins could be improved by attenuating the PEG-related immune response. On the other hand, anti-PEG immune responses might be exploited for vaccine applications. Our recent studies demonstrated that anti-PEG antibodies mediate the delivery of antigens encapsulated in PEGylated liposomes, and enhance antigen-specific immune responses. In this review, we summarize anti-PEG antibody induction by PEGylated proteins and alterations in anti-PEG IgM-mediated pharmacokinetics and pharmacodynamics. These findings extend our knowledge of PEG-related immune responses.

Herein, we investigated the pharmacokinetic (PK) profile of nedaplatin (cis-diamine-glycolateplatinum; CDGP) in a hemodialysis (HD) patient with advanced esophageal squamous cell carcinoma (ESCC) by administering the CDGP immediately prior to HD. Our patient was treated with CDGP (45 mg/m 2 for a total dose of 60.2 mg) and 5-fluorouracil (560 mg/m 2 for a total dose of 750 mg) before initiating HD. The total platinum (Pt) concentration (Pt &#95;total ) and free Pt concentration (Pt &#95;free ) 2 h after completion of HD were 0.4 μg/mL and 0.3 μg/mL, respectively. The removal rates of Pt &#95;total and Pt &#95;free by the dialyzer were 76.5% and 84.6%, respectively. Twenty-four hours after CDGP administration, the Pt &#95;free was below the detection limit of the method of analysis. Pt &#95;free within the range of the recommended CDGP target AUC 0-24 was 8-10 μg/mL•h, the AUC 0-24 of Pt &#95;total and Pt &#95;free were 16.5 μg/mL•h and 8.8 μg/mL•h, respectively. We conclude that HD should be performed after the end of CDGP infusion as part of the CDGP chemotherapy regimen for HD patients with ESCC, and suggest that HD is effective for obtaining a PK profile of CDGP similar to patients with normal renal function.

Pharmacometrics is the mathematical study of pharmacokinetics, disease progression, and clinical outcomes. One objective of pharmacometrics is to facilitate rational drug treatment in patients, also termed clinical pharmacometrics. In this review, our clinical pharmacometric studies conducted over the last 10 years are discussed. Population pharmacokinetic analysis using therapeutic monitoring data for levetiracetam revealed that oral clearance allometrically scaled to both body weight and estimated glomerular filtration rate can accurately predict clinical data from patients of various ages (pediatric to elderly) with varying renal function. Dosage adjustments based on renal function in the package information are effective in controlling the trough and peak concentrations in similar ranges. In addition, a retrospective pharmacokinetic and pharmacodynamic study revealed that the efficacy of low-dose clobazam therapy was significantly influenced by CYP2C19 polymorphisms. Pharmacokinetic and pharmacodynamic models were successfully built using electronic medical information to explain retrospective international normalized ratio values of prothrombin time before and after catheter ablation in warfarin-treated patients. Simulation studies suggest that more than 20 mg of vitamin K 2 is unnecessary in the preoperative period of catheter ablation. A physiologically based pharmacokinetic model adapted to tacrolimus pharmacokinetic data in patients who underwent living-donor liver transplantation was constructed, and clarified that oral clearance of this drug was affected by CYP3A5 genotypes in both the liver and intestine to the same extent. In conclusion, pharmacometrics is a useful methodology for individualized and optimized drug therapy.

Drug transporters play important roles in determining drug pharmacokinetics. Organic anion transporting polypeptides 1B1/1B3 (OATP1B1/1B3) are transporters mediating hepatic uptake of various anionic drugs. OATP1B1/1B3 activities are changed by genetic mutation and drug-drug interaction (DDI) that could lead to severe adverse reactions. Methods to address the precise DDI risk assessment have been developed in addition to the translational assessment from the results of in vitro studies. Using endogenous substrates as probes is an emerging approach that allows clinical assessment of the DDI risk in the early phase of drug development. Then, the clinical data will be subjected to the pharmacokinetic analysis using physiologically-based pharmacokinetic models to perform the more realistic DDI risk assessment with OATP1B1/1B3 substrate drugs. When drug targets are located inside the hepatocytes, DDI impact on the intrahepatic concentration is critical for their pharmacological actions. Positron emission tomography (PET) allows researchers to determine tissue concentration time profiles of the PET probe upon the inhibition of OATP1B1/1B3, and to estimate the change in kinetic parameter for each intrinsic process of hepatic elimination of PET probe. Integration of the clinical data into the PBPK model realizes more precise prediction of DDI impact on the pharmacokinetics of drugs, and their therapeutic effects.

MPS (microphysiological system) is in-vitro cell-culture environment, which is precisely maintained in a micro space manufactured using MEMS (micro electro mechanical systems) technology, to derive in-vivo like functions from human cells. From the viewpoint of pharmacokinetics, it can be considered as a wet PBPK/PD simulator consisting of the micro organs (cell culture units) connected each other with a circulating medium, which mimic the organs responsible for the drug's ADME (absorption-distribution-metabolism-elimination). In this review, we identify two types of the cell culture units consisting of the MPS for pharmacokinetics, and overview the characteristics of each type. Then, we discuss about the technical requirements needed for the cell culture unit from the point of view of both cell-culture environmental design and cell function, and introduce the world-wide current situation of the commercialization of the MPS.

Quantitative systems pharmacology (QSP) is an emerging field of modeling technologies that describes the dynamic interaction between biological systems and drugs. Recently, QSP is increasingly being applied to pharmaceutical drug discovery and development, and used for various types of decision makings. In contrast to empirical and statistical models, QSP represents complex systems of human physiology by integrating comprehensive biological information, hence, it can address various purposes including target and/or disease-related biomarker identification, hypothesis testing, and prediction of clinical efficacy or toxicity. On the other hand, structures of QSP models become quite complicated with huge amount of biological components, therefore, close collaboration between pharmacologists having profound knowledge of biology and drug metabolism and pharmacokinetics (DMPK) scientists, experts of model building, is crucial for QSP development and implementation. This article introduces, from DMPK scientists to pharmacologists, main features of QSP and its applications in pharmaceutical industries, and discusses challenges and future perspectives for effective utilization in drug discovery and development.

In drug disposition, the liver and small intestine are very important as tissues involving in drug metabolism, absorption, and excretion. Thus, in drug development studies, it is necessary to evaluate the pharmacokinetics in these tissues accurately including the contributions of drug-metabolizing enzymes and drug transporters. Currently, all kinds of evaluation systems have been used for the pharmacokinetic prediction; however, there are some issues in these systems. Therefore, the researches for the development of human induced pluripotent stem (iPS) cell-derived hepatocytes and enterocytes, as novel systems besides existing ones, are being advanced. Because human iPS cells have abilities of pluripotency and almost infinite proliferation, it is thought to be possible to stably provide the high-quality cells that have similar characteristics to human normal tissue cells by using human iPS cells. In this review, we describe current status of differentiation studies of human iPS cell-derived hepatocytes and enterocytes and the functional characteristics of these cells centered on pharmacokinetic functions.

To administer optimal and safe pharmacotherapy, development of stratified and personalized therapy is imperative. Pharmacogenomics (PGx) is useful in elucidating factors causing individual differences in drug efficacy and the emergence of adverse effects. It also helps design accurate drug administration methods by evaluating the effects of patient-related factors, such as genetic factors, that influence pharmacokinetics (PK) and pharmacodynamics (PD). In addition, selection of appropriate therapeutic agents requires the implementation of precision medicine allowing accurate disease diagnosis. To establish precision medicine, it is necessary to uncover the association of pathophysiological factors, which are represented as endotype or genotype, with the pathology of several phenotypes. This review describes two aspects related to realization of individualized medicine, namely the effectiveness of PK/PD/PGx studies and the stratification of pathological conditions. First, we conducted a PK/PD/PGx study with the aim to individualize warfarin treatment. In this study, we elucidated the effect of CYP4F2 polymorphisms associated with vitamin K metabolism by measuring the blood concentrations of warfarin and vitamin K. Then, to develop precision medicine for asthma and chronic obstructive pulmonary disease (COPD), we analyzed not only clinical symptoms but also pathological biomarkers and genes associated with inflammation. The findings may contribute toward better understanding of the pathological conditions of asthma, COPD, and asthma-COPD overlap.

The abuse of drugs has become a serious social problem worldwide. Amphetamine-type stimulants such as methamphetamine are recreationally abused and can cause toxic effects in the body. Unfortunately, death from drug poisoning can occur due to careless intake. In postmortem examinations, the distribution of drugs in an entire organ gives valuable information for evaluating their toxicity. We developed methods to measure the distribution of drugs in organs using LC/MS and matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). The complementary use of the two methods provides more detailed information on the distribution and concentration of drugs in organs because the accurate quantification in LC/MS and small spatial resolution in MALDI-IMS are combined. On the other hand, it is important to elucidate the drug intake history of suspects and victims in drug-facilitated crimes (DFCs). Hair and nail samples are often used to confirm chronic drug intake because ingested drugs can stably remain in these specimens over several months. However, it is impossible to determine the day of drug ingestion in conventional segmental analysis of bulk samples. Therefore, we developed methods to cut hair strands at 0.4-mm intervals and nails at 0.2-mm intervals, which correspond to their respective growth rates over 1-2 d, to analyze the drugs in each segment efficiently using LC/MS. The microsegmental hair analysis method is applied to estimate the day of drug ingestion in DFC investigations. These methods could be applied to measure the distribution of compounds in various solid samples.

When considering the use of pharmaceutical drugs during pregnancy and lactation, two concerns must be weighed against each other: the potential deleterious effects on the fetus and the possibility that treatment necessary for the woman but risky for the fetus either cannot be administered or else the woman must give up the pregnancy or give up nursing. The main roadblock to weighing these two concerns is a lack of evidence about what drugs are harmful to the fetus. Establishing this evidence is important to implementing the "Choosing Wisely" policy. In 2005, Japan established the Japan Drug Information Institute in Pregnancy (JDIIP), which addresses issues regarding treatments with pharmaceutical drugs during pregnancy and lactation. The JDIIP has analyzed data regarding the pregnancy results of patients who have received counseling and has conducted a registration survey, analyzed post-marketing survey data from pharmaceutical companies, and measured drug concentrations in breast milk. Currently, the JDIIP is increasing the number of targeted drugs about which it is collecting evidence. In addition, it is re-evaluating the published literature and implementing a project to revise drug packaging inserts. Pharmacists are expected to implement the "Choosing Wisely" policy regarding pharmaceutical treatment during pregnancy and lactation and to contribute to the collection of new evidence.

Over the past few decades, liposome drug delivery systems (liposome DDS) have attracted much attention as the most advanced DDS. Efficacy and toxicity profiles of liposomes are based on their characteristic pharmacokinetics, drug release, and disposition after administration. Many attempts have been made to develop these systems especially as liposomal anti-cancer drugs. In the development of liposome DDS, identification of critical quality attributes and establishment of a control strategy to ensure consistent drug product quality are crucial. Among the quality attributes, particle size, drug encapsulation, and drug release from liposomes would affect their in vivo pharmacokinetic and pharmacodynamic properties. Thus these features need to be evaluated with appropriate analytical methods to confirm the quality and performance of the drug products. This article focuses on drug release from liposomes and reviews the effects of physicochemical properties of loaded drugs on release, simulation of drug release from liposomes, and design of a simulated body fluid for drug release assay of drug products.