5-fluorouracil (5-FU) is a cytotoxic antimetabolite that interferes with nucleic acid metabolism in both normal and cancer cells. Capecitabine is a prodrug of 5-FU, and S-1 is an oral 5-FU derivative. Patients usually tolerate treatment with one fluorouracil drug well. However, simultaneous application of two or more fluorouracil drugs such as capecitabine and S-1 can lead to life-threatening toxicities.

A 73-year-old male with gastric and rectal cancer was admitted to the emergency department because of severe oral mucositis, hand-foot syndrome, and fever after concurrently taking capecitabine (1.5 g twice a day) and S-1 (50 mg twice a day) for 3 days at home. He was immediately given recombinant human granulocyte colony-stimulating factor (200 mg SC once a day) and recombinant human thrombopoietin (15,000 IU SC once a day). Hemagglutinin (1 unit IM once a day) was administered. Anti-infection and mucosal care were started promptly. A few days later, he developed supraventricular premature beats and short flutter requiring cardioversion. After comprehensive treatment, the patient’s infection was effectively controlled, and mucosal damage and cardiac toxicity were significantly alleviated.

5-FU overdose caused by the combination of capecitabine and S-1 can cause serious adverse reactions. Careful checking of the medical orders and extensive education of patients to recognize the symptoms of toxicity may reduce the occurrence of such adverse reactions.

5-FU overdose caused by the combination of capecitabine and S-1 can cause serious adverse reactions. Careful checking of the medical orders and extensive education of patients to recognize the symptoms of toxicity may reduce the occurrence of such adverse reactions.

We attempted to examine the applicability of a population pharmacokinetic-pharmacodynamic (PK-PD) model describing the metabolic interaction between warfarin and sorafenib due to CYP2C9 inhibition and to predict the plasma concentrations of sorafenib and S-warfarin, the international normalized ratio (INR), and the optimal maintenance dose of warfarin in the presence of sorafenib in vivo.

The sorafenib inhibition constant for S-warfarin metabolism was determined in vitro, and the unbound fraction in the liver was estimated using the published equations. A population PK-PD model describing the interaction between warfarin and sorafenib assuming competitive metabolic inhibition of S-warfarin by sorafenib was developed using NONMEM. The model was evaluated using clinical data and INR collected from the literature.

The observed time courses of INR retrieved from Japanese and Caucasian patients given warfarin and sorafenib were mostly within the 90% range of the predicted values. Then, we predicted the plasma sorafenib and S-warfarin concentrations and INR after administration of warfarin (3mg/day) alone and warfarin + sorafenib (800mg/day). The predicted mean plasma S-warfarin concentration and INR at steady state were almost 6 and 2times greater, respectively, in the presence of sorafenib than those for warfarin alone. The predicted S-warfarin concentrations and INR after reduction of the warfarin dose (0.5mg/day) in the presence of sorafenib were comparable to those after 3mg/day warfarin alone.

The proposed population PK-PD model has the potential to predict an increase in INR quantitatively after concurrent administration of warfarin and sorafenib.

The proposed population PK-PD model has the potential to predict an increase in INR quantitatively after concurrent administration of warfarin and sorafenib.Acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread rapidly in numerous countries and caused a massive number of deaths. Interferon-α (IFN-α), lopinavir/ritonavir, chloroquine phosphate, arbidol, ribavirin, remdesivir, and dexamethasone are the therapeutic drugs recommended for treating 2019-nCoV disease (COVID-19 disease). Due to the particularity of immune function, pregnant women seem to be more susceptible to the virus. We searched the literature to find effective and safe drugs for patients with COVID-19 during pregnancy and to provide drug therapy strategies for medical staff. According to the current literature we reviewed, we suggest that IFN-α and arbidol can be retained in the treatment regimen for pregnant women and that to reduce maternal mortality, appropriate doses of dexamethasone can be given to those who are predicted to have low premature survival and to receive mechanical ventilation or oxygen. However, the use of dexamethasone in the 1st trimester and after 37 weeks of gestation should be avoided.

A possible correlation between caffeine and coronary heart disease (CHD) is controversial. The objective of this study was to explore the effect of long-term inhalation of caffeine-sodium benzoate (CSB) on the development of CHD in men, the severity of coronary artery lesions and the possible contributing effects of smoking.

A retrospective analysis was performed on 2,001 consecutive men who underwent selective coronary angiography. These men were assigned to a CSB inhalation group (CSB; 1-6 times/d, 274-1,644mg/d, >10years; n=326) or a non-inhalation group (non-CSB; n=1,675).

The two groups were compared for the prevalence, onset age, and risk factors of CHD. The men were also stratified as CSB-only, smoking-only, combined CSB+ smoking, and the control (non-CSB+non-smoking). The prevalence, onset age, risk factors of CHD, and severity of coronary artery lesions and major adverse cardiovascular events (MACE) were compared among these groups.

The prevalence of CHD in the CSB group was higher compared with the non-CSB group (91.72 vs. 86.09%, p<0.01). In the CSB+smoking group, the percentages of men with CHD (93.11%) or >70% stenosis of the coronary artery lesion (64.92%) were significantly higher than that of the smoking-only group (88.19 and 54.29%, respectively) or control (83.20 and 52.90%), while the percentage with stenosis involving the anterior descending branch was lower (62.30 vs. 72.29% and 74.17%, p<0.01).

Men who inhaled CSB long-term had a higher rate of CHD compared with those who did not take CSB. The combination of CSB inhalation and smoking appears to increase synergistically the risk and severity of CHD.

Men who inhaled CSB long-term had a higher rate of CHD compared with those who did not take CSB. The combination of CSB inhalation and smoking appears to increase synergistically the risk and severity of CHD.

To assess the relative efficacy and safety of biological agents in patients with systemic juvenile idiopathic arthritis (sJIA).

We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of canakinumab, anakinra, tocilizumab, and rilonacept in patients with sJIA.

Five RCTs that included 286 patients met the inclusion criteria. Canakinumab was the most effective treatment for sJIA (odds ratio, 55.04; 95% credible interval, 15.52 – 253.29). A greater efficacy was observed with canakinumab than with tocilizumab and rilonacept. All interventions achieved a significant modified American College of Rheumatology Pediatric 30 (ACRpedi30) response compared to the placebo. The ranking probability, based on the surface under the cumulative ranking curve, indicated that canakinumab had the highest probability of being the best treatment in terms of the modified ACRpedi30 response rate, followed by anakinra, tocilizumab, rilonacept, and the placebo. However, no significant differences were observed in the incidence of serious adverse events after treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo.

In patients with sJIA, canakinumab had the highest probability of being the best treatment in terms of the modified ACRpedi30 response rate; neither of the tested biological agents were associated with a significant risk of serious adverse events.

In patients with sJIA, canakinumab had the highest probability of being the best treatment in terms of the modified ACRpedi30 response rate; neither of the tested biological agents were associated with a significant risk of serious adverse events.

Discoid lupus erythematosus (DLE) is a common manifestation of lupus erythematosus. Hydroxychloroquine is commonly used in the treatment of lupus erythematosus. The present study aims to report hallucinations induced by hydroxychloroquine.

A 37-year-old woman came to the dermatology clinic with a complaint of a red lesion on her left cheek. Physical examination revealed an ulcerative erythematous plaque with keratotic scales, an atrophic area of ~2×2.5cm. Biopsy of the lesion was performed, and histopathology result was consistent with the diagnosis of DLE. Laboratory tests were all normal. Topical clobetasol and pimecrolimus were prescribed for the patient, who was recommended to use sunscreen as well. However, the treatment did not work, thus hydroxychloroquine 200mg daily was added to the treatment. After a week, the patient came back to the clinic with her husband with the complaint of auditory and visual hallucinations, nightmares, and occasional decrease in consciousness level. After neurology and pwidely used in the treatment of COVID-19 and other diseases, its potential risk of psychiatric complications should be considered in clinical practice.

The contribution ratios (CR) of metabolic enzymes to the systemic clearance of a drug can be estimated from in vitro studies. Another feasible approach is to calculate them based on the increase in the area under the time-concentration curve (AUC) caused by the co-administration of a potent and selective inhibitor in a clinical drug-drug interaction (DDI) study. However, some factors, such as the inhibitory potency of the inhibitor and the inhibition of first-pass metabolism, might affect the estimation of CR based on clinical DDI studies. We aimed to validate the accuracy of the DDI-based estimation of CR using an in silico approach.

An in silico DDI study was conducted using a population-based physiological pharmacokinetic simulator to estimate the CR of cytochrome P450 (CYP)3A4 for zolpidem, sildenafil, omeprazole, triazolam, and repaglinide. The ratio of the AUC value seen in the presence of an inhibitor (ketoconazole or itraconazole) to that observed in the absence of the inhibitor (AUC ratio) was also calculated. The CR for CYP3A4 obtained using the simulator (CR

) were compared with those calculated from the AUC ratio (CR

).

When ketoconazole was used, good correlations between the CR

and CR

were obtained for all examined substrates (inconsistencies were seen in < 10% of subjects). CR estimates derived from the AUC ratio were found to be accurate. Some underestimation was observed, possibly due to incomplete inhibition, and some overestimation caused by extensive first-pass metabolism was noted.

This study verified that CR obtained from AUC ratios in DDI studies are quite reliable.

This study verified that CR obtained from AUC ratios in DDI studies are quite reliable.

This study aimed to compare the rate of hypoglycemic events from all spontaneously reported adverse events (AEs) between insulin detemir and insulin degludec using the Korea Adverse Event Reporting System (KAERS) database.

We analyzed data on the reported hypoglycemia events retrieved from adverse drug reactions (ADR) on the use of different insulin types from 2016 to 2017 in the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). After defining hypoglycemic events as the AE of interest, we performed a disproportionality analysis by calculating the reporting odds ratio (ROR) to identify the disproportionality of AEs following treatment with insulin degludec (IDeg) and insulin detemir (IDet). Because spontaneously reported hypoglycemic events were not distinguished between insulin glargine 100U/mL (Gla-100) and insulin glargine 300U/mL (Gla-300) due to same ATC code by KIDS-KD, direct comparisons of Gla-100 and Gla-300 or comparisons of each analog of insulin glargine vs.