Chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT) have an increased risk of cardiovascular disease (CVD). Cinacalcet is a calcimimetic that permits impaired endothelial functions to be recovered via inhibiting parathyroid hormone (PTH) production in SHPT patients. However, the underlying mechanism for its action remains unknown. The purpose of this study was to examine the effect of cinacalcet on the redox state of human serum albumin (HSA), a reliable marker for assessing endothelial oxidative damage in SHPT patients who were receiving hemodialysis. Cinacalcet was administered to six SHPT patients for a period of 8 weeks. After 4 weeks of treatment, cinacalcet significantly decreased the oxidized albumin ratio which is a ratio of reduced and oxidized forms of HSA via increasing reduced form of HSA. Moreover, the radical scavenging abilities of HSA that was isolated from SHPT patients were increased by cinacalcet, suggesting the recovery of the impaired vascular anti-oxidant ability. Interestingly, the oxidized albumin ratio in SHPT patients was significantly higher than that in hemodialysis patients. In addition, the changes of intact PTH levels were significantly correlated with the oxidized albumin ratio. It therefore appears that PTH may induce oxidative stress in SHPT patients. In fact, an active analogue of PTH increased the production of reactive oxygen species in human endothelial cells. Thus, cinacalcet exhibits anti-oxidative activity through its pharmacological action. Additionally, cinacalcet itself showed radical scavenging activity. In conclusion, cinacalcet improves the redox status of HSA by inhibiting PTH production and partially by its radical scavenging action.

It has long been suggested that a Na⁺-dependent carrier-mediated transport system is involved in the absorption of nucleobases and analogs, including some drugs currently in therapeutic use, for their uptake at the brush border membrane of epithelial cells in the small intestine, mainly based on studies in non-primate experimental animals. The presence of this transport system was indeed proved by the recent identification of sodium-dependent nucleobase transporter 1 (SNBT1/Slc23a4) as its molecular entity in rats. However, this transporter has been found to be genetically deficient in humans and higher primates. Aware of this deficiency, we need to revisit the issue of the absorption of these compounds in the human small intestine so that we can understand the mechanisms and gain information to assure the more rational use and development of drugs analogous to nucleobases. Here, we review the current understanding of the intestinal absorption of nucleobases and analogs. This includes recent knowledge about the efflux transport of those compounds across the basolateral membrane when exiting epithelial cells, following brush border uptake, in order to complete the overall absorption process; the facilitative transporters of equilibrative nucleoside transporter 1 (ENT1/SLC29A1) and equilibrative nucleobase transporter 1 (ENBT1/SLC43A3) may be involved in that in many animal species, including human and rat, without any major species differences.

Vascular dementia (VD) is a common neurodegenerative disease, and the cognitive dysfunction is a major manifestation of VD. Lots of evidences showed that beta-amyloid (Aβ) deposition and neuroinflammation act as vital elements in the progress of VD. The previous studies showed that osthole (OST) can improve the cognitive function of VD and Alzheimer’s disease (AD). However, the effect of OST on Aβ in VD brain is still unclear. Chronic cerebral hypoperfusion (CCH) of rats were used to investigate the effect of OST on Aβ through nod-like receptor protein 3 (NLRP3) inflammasome in this study. Morris Water Maze and Y-maze were used to test the spatial learning, memory and working abilities. Hematoxylin–eosin (H&E) and Nissl staining were used to observe the morphology and number of hippocampal neurons. Immunofluorescence staining was used to observe the number of microglia activated. Western blot was used to detect the expression of proteins. The study results showed that OST obviously enhanced the spatial learning, memory and working abilities induced by modified bilateral common carotid artery occlusion (BCCAO) in rats, improved the pathological damage of hippocampal neurons induced by BCCAO in rats, inhibited the activation of microglia induced by BCCAO in rats. Furthermore, this study also discovered that OST reduced Aβ deposition in VD hippocampus via inhibition the NLRP3 inflammasome. Together, these results suggest that OST reduces Aβ deposition via inhibition NLRP3 inflammasome in microglial in VD.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium, and it is found in many foods. Acrylamide (AA) can be produced in foods treated at high temperatures. In this study, we investigated the combined toxicity of OTA and AA against human renal and hepatic cells in vitro. The concentration at which the synergistic effect of OTA and AA occurs was determined using the combination index obtained from the cell viability results for OTA and AA individually or in combination. The synergistic toxicity of both substances was evaluated by cell viability and the production of reactive oxygen species. In addition, apoptosis-related markers were significantly upregulated by OTA and AA individually or in combination. To determine the combined toxic effects of OTA and AA on the cells, the levels of enzymes involved in the phase I reaction and apoptosis-related markers were determined using quantitative (q)PCR and Western blot. The expression levels of CYP enzymes CYP1A1 and CYP1A2 involved in the phase I reaction significantly increased when the cells were treated with OTA and AA in combination. The expression of apoptosis-related markers, Bcl2-associated X protein (Bax) and caspase 3, also increased when the cells were treated with OTA and AA in combination. Therefore, the synergistic toxicity of OTA and AA suggests that such effects may contribute to nephrotoxicity and hepatotoxicity.

Crocetin is a major bioactive ingredient in saffron (Crocus sativus L.) and has favorable cardiovascular effects. Here, the effects of crocetin on L-type Ca²⁺ current (I_Ca-L), contractility, and the Ca²⁺ transients of rat cardiomyocytes, were investigated via patch-clamp technique and the Ion Optix system. A 600 µg/mL dose of crocetin decreased I_Ca-L 31.50 ± 2.53% in normal myocytes and 35.56 ± 2.42% in ischemic myocytes, respectively. The current voltage nexus of the calcium current, the reversal of the calcium current, and the activation/deactivation of the calcium current was not changed. At 600 µg/mL, crocetin abated cell shortening by 28.6 ± 2.31%, with a decrease in the time to 50% of the peak and a decrease in the time to 50% of the baseline. At 600 µg/mL, crocetin abated the crest value of the ephemeral Ca²⁺ by 31.87 ± 2.57%. The time to half maximal of Ca²⁺ peak and the time constant of decay of Ca²⁺ transient were both reduced. Our results suggest that crocetin inhibits L-type Ca²⁺ channels, causing decreased intracellular Ca²⁺ concentration and contractility in adult rat ventricular myocytes. These findings reveal crocetin's potential use as a calcium channel antagonist for the treatment of cardiovascular disease.

Early diagnosis of Niemann–Pick diseases (NPDs) is important for better prognosis of such diseases. N-Palmitoyl-O-phosphocholine-serine (PPCS) is a new NPD biomarker possessing high sensitivity, and with its combination with sphingosylphosphocholine (SPC) it may be possible to distinguish NPD-C from NPD-A/B. In this study, a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method (method 1) and a validated LC-MS/MS analysis (method 2) of PPCS and SPC were developed, and we have proposed a diagnostic screening strategy for NPDs using a combination of serum PPCS and SPC concentrations. Nexera and API 5000 were used as LC-MS/MS systems. C18 columns with lengths of 10 and 50 mm were used for method 1 and 2, respectively. ²H₃-Labeled PPCS and nor-SPC were used as internal standards. Selective reaction monitoring in positive-ion mode was used for MS/MS. Run times of 1.2 and 8 min were set for methods 1 and 2, respectively. In both methods 1 and 2, two analytes showed high linearity in the range of 1–4000 ng/mL. Method 2 provided high accuracy and precision in method validation. Serum concentrations of both analytes were significantly higher in NPD-C patients than those of healthy subjects in both methods. Serum PPCS correlated between methods 1 and 2; however, it was different in the case of SPC. The serum PPCS/SPC ratio was different in healthy subjects, NPD-C, and NPD-A/B. These results suggest that using a combination of the two LC-MS/MS analytical methods for PPCS and SPC is useful for diagnostic screening of NPDs.

Gene and nucleic medicines have recently gained attention as novel drugs with the advancement of molecular biology and genetics; however, they have low bioavailability and low target delivery due to their low stability and poor membrane permeability. Therefore, the development of an effective drug delivery system (DDS) is necessary for the practical use of gene and nucleic acid medicines; however, despite considerable research, both safety and efficiency remain poor. Furthermore, the healthcare needs are not met by traditional DDS. Therefore, we developed an effective multi-functional DDS, which is constructed using materials that are safe for human consumption. This DDS involves several ternary complexes as novel gene delivery carriers constructed by coating the cationic complex of the gene and nucleic acid medicines as well as the biodegradable cationic polymer with a biocompatible anionic polymer. Early implementation of the ternary complex in clinical studies is expected due to their efficacy and safety. Furthermore, these complexes may be prepared using large-scale manufacturing. In addition, personalized DDS may be prepared according to the patient’s disease stage, which is useful for advanced therapy.

The sodium salt of isosteviol (STVNa) is a beyerane diterpene synthesized through acid hydrolysis of stevioside. STVNa improves multiple types of tissue injuries. However, it is not known how isosteviol sodium affects high-fat and high cholesterol diet (HFD)-induced kidney. Therefore, in this study we examined the potential molecular mechanism underlying STVNa mediated protective effect against high fat/high cholesterol-induced kidney dysfunction in HFD-induced kidney injury. Sprague-Dawley (SD) rats were allocated into six groups: the normal group, HFD group and HFD treated with three doses of STVNa, fenofibrate treatment group. The results indicated that HFD induced kidney injury evident by a 60% increase in serum creatinine (CRE) leves. In addition, there was a significant accumulation of triglycerides (approx. 60%), fatty acids (approx. 50%) and total cholesterol (approx. 2.5 fold) in the kidneys. STVNa inhibited HFD-induced kidney injury evident by reducing the increased levels of serum CRE. Specifically, STVNa attenuated HFD-induced kidney injury by inhibiting inflammation, oxidative stress, and apoptosis. These findings indicate that STVNa has a therapeutic potential for HFD-induced kidney dysfunction. The mechanisms of this pharmacological effect are through the inhibition of inflammation, oxidative stress and apoptosis.

The immunostimulatory activity of unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) could be improved via delivery to immune cells expressing Toll-like receptor 9 (TLR9). Previously, we showed that the polypod-like structured nucleic acid (polypodna), a nanostructured DNA comprised of three or more ODNs, was an efficient system for the delivery of CpG ODNs to immune cells. Because some TLR9-positive immune cells express mannose receptors (MR), the uptake of polypodna by immune cells can be further increased by its modification with mannose. In this study, we selected the phosphodiester CpG ODN, ODN1668, which has a sequence identical to CpG1668, and a hexapodna, a polypodna with six pods, to design a hexapodna that harbored ODN1668 or the mannosylated CpG ODN (Man-ODN1668) synthesized via modification of the 5′-terminal of ODN1668 with a synthesized mannose motif. By mixing ODN1668 or Man-ODN1668 with the hexapodna, ODN1668/hexapodna and Man-ODN1668/hexapodna were successfully formed with high yields. However, Man-ODN1668/hexapodna was found to induce a greater tumor necrosis factor-α release from TLR9- and MR-positive mouse peritoneal macrophages and macrophage-like J774.1 cells than Man-ODN1668 or ODN1668/hexapodna. These results indicate that the combination of mannose modification and incorporation into nanostructured DNA is a useful approach for enhancing the immunostimulatory activity of CpG ODN.

The detailed epidemiology of invasive mycoses and superficial mycoses has not been clarified in Japan. In addition, treatment options have increased because of novel antifungals and/or guidelines for fungal infection. In the present study, we aimed to clarify the trends of antifungal use in Japan from 2006 to 2015 based on sales data to serve as an alternative indicator of fungal infection trends. We found that the total antifungal use decreased over time (r = −0.057, P_{for trend} < 0.0001). Oral and parenteral use significantly decreased by 44.1% (r = −0.056, P_{for trend} < 0.0001) and 27.1% (r = −0.0012, P_{for trend} = 0.00061), respectively. The trend of antifungal use for superficial mycoses significantly decreased by 49.8% (r = −0.061, P_{for trend} < 0.0001). However, the trend of antifungal use for invasive mycoses was significantly increased by 19.9% (r = 0.0032, P_{for trend} = 0.00045). In Japan, the increase in the number of immunocompromised patients might be associated with the increase in the frequency of antifungal use for invasive mycoses. This is the first study to clarify the trends of antifungal use in Japan. Further research is needed to establish a continuous surveillance system to compare fungal infections between Japan and the world.

A genetically modified (GM) soybean kernel detection system using combination of DNA preparation from individual soybean kernels and event-specific real-time PCR was developed to simultaneously identify GM soybean events authorized for food after safety assessments in Japan. Over 100 kernels in the non-identity-preserved soybean samples imported from the United States of America (two U.S.A. lots) and Brazil (one lot) were randomly selected and examined. In total, 98 and 96% of the two independent U.S.A. lots, and 100% of the Brazilian lot contained GM soybean kernels. Herbicide-tolerant events, MON89788 (trade name Genuity^® Roundup Ready 2 Yield™), GTS 40-3-2 (trade name Roundup Ready™ soybean) and A2704-12 (trade name Liberty Link^® soybean), were detected similarly in both U.S.A. lots. In the Brazilian lot, in addition to GTS 40-3-2, a stacked GM event, MON87701 × MON89788, having insect-resistance and herbicide-tolerance, was detected. There were no unauthorized GM soybeans comingled, and the ratio of GM soybean events detected was consistent with statistical reports on the cultivated GM soybean events in both countries.

This study aims to evaluate the association between passive smoking and high-grade squamous intraepithelial lesion (HSIL) at the sample of Chinese women. We conducted a case-control study to analyze the effect of passive smoking on the incidence that patients diagnosed with HSIL. The participants had undergone cervical cancer screening by cytology and human papillomavirus (HPV) co-testing within a year before the study. Multiple logistic regression was used to explore the effect and interactive effect of risk factors on HSIL. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Passive smokers were 1.57 times (95% CI 1.05–2.35) higher than non-smokers to occur HSIL. The medium of the combined smoking index divided patients into low and high exposure, with the ORs of 1.64 (95%CI 1.02–2.64) and 1.71 (95%CI 1.06–2.77) relative to non-smokers, respectively. The combined smokers in the high exposure group experienced the most considerable risk of HSIL (OR = 4.67; 95%CI 1.17–18.70). The OR of HPV positive passive smoker relative to that of HPV negative non-smokers was 5.28 (95%CI 2.25–14.52;). Passive smokers who reported adolescent exposure history was 4.04 times (95%CI 1.44–11.37) more at risk of the disease than non-smokers. This study supported that passive smoking was a significant independent risk factor on the occurrence of HSIL and showed a positive correlated dose-response relationship. HPV infection interacting with passive smoking led to an even higher risk of the disease. Adolescent exposure to passive smoking persistent for more than 20 years would also increase the risk of HSIL.

Latifolin, a natural flavonoid found in Dalbergia odorifera T. Chen, has been reported to exhibit anti-inflammatory and anticarcinogenic activities in vitro. However, the anti-aging effects of latifolin are unknown. In this study, we selected a model in vitro system, hydrogen peroxide (H₂O₂)-induced senescence in human dermal fibroblasts (HDFs), to examine the protective effects of latifolin against senescence and the detailed molecular mechanisms involved. Latifolin reversed the senescence-like phenotypes of the oxidant-challenged model, including senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation, and the expression of senescence-related proteins, such as caveolin-1, ac-p53, p21^Cip1/WAF1, p16^Ink4α, pRb, and cyclinD1. We also found that latifolin induced the expression of silent information regulator 1 (SIRT1) in a concentration- and time-dependent manner, and the anti-senescence effect of latifolin was abrogated by SIRT1 inhibition. Latifolin also suppressed the activation of Akt and S6K1 and attenuated the increase in SA-β-gal activity after H₂O₂ exposure. Our results indicate that latifolin exerts protective effects against senescence in HDFs and that induction of SIRT1 and inhibition of the mammalian target of rapamycin (mTOR) pathway are key mediators of its anti-aging effects.

Patients with cholestatic liver diseases, such as primary biliary cirrhosis, usually suffer from pruritus. However, the pathogenesis of cholestatic pruritus is unclear, and there is no current effective treatment for it. In order to find a treatment for the condition, an appropriate mouse model should be developed. Therefore, here, we established a surgically-induced mouse model of cholestatic pruritus. The bile duct was ligated in order to block bile secretion from the anterior, right, and left lobes, with the exception of the caudate lobe. Serum levels of total bile acid increased after bile duct ligation (BDL). The spontaneous hind paw scratching was also increased in BDL mice. Spontaneous scratching was reduced in BDL mice by naloxone (µ-opioid receptor antagonist), U-50,488H (κ-opioid receptor agonist), and clonidine (α2-adrenoceptor agonist). Azelastine (H₁ receptor antagonist with membrane-stabilizing activity) slightly reduced scratching. However, terfenadine (H₁ receptor antagonist), methysergide (serotonin (5-HT)₂ receptor antagonist), ondansetron (5-HT₃ receptor antagonist), proteinase-activated receptor 2-neutralizing antibody, fluvoxamine (selective serotonin reuptake inhibitor), milnacipran (serotonin-noradrenalin reuptake inhibitor), and cyproheptadine (H₁ and 5-HT₂ receptor antagonist) did not affect scratching. These results suggested that partial obstruction of bile secretion in mice induced anti-histamine-resistant itching and that central opioid system is involved in cholestatic itching.

Large conductance Ca²⁺-activated K⁺ (BK_Ca) channels are ubiquitously expressed in plasma membrane of both excitable and non-excitable cells and possess significant physiological functions. A tetrameric complex of α subunit (BKα) forms a functional pore of BK_Ca channel. The properties of BK_Ca channel, such as voltage-dependence, Ca²⁺ sensitivity and pharmacological responses, are extensively modulated by co-expressing accessory β subunits (BKβ), which can associate with BKα in one to one manner. Although the functional significance of newly identified γ subunits (BKγ) has been revealed, the stoichiometry between BKα and BKγ1 remains unclear. In the present study, we utilized a single molecule fluorescence imaging with a total internal reflection fluorescence (TIRF) microscope to directly count the number of green fluorescent protein (GFP)-tagged BKγ1 (BKγ1-GFP) within a single BK_Ca channel complex in HEK293 cell expression system. BKγ1-GFP significantly enhanced the BK channel activity even when the intracellular Ca²⁺ concentration was kept lower, i.e., 10 nM, than the physiological resting level. BKγ1-GFP stably formed molecular complexes with BKα-mCherry in the plasma membrane. Counting of GFP bleaching steps revealed that a BK_Ca channel can contain up to four BKγ1 per channel at the maximum. These results suggest that BKγ1 forms a BK_Ca channel complex with BKα in a 1 : 1 stoichiometry in a human cell line.

Rotavirus (RV) induced diarrhea has been a major reason affecting children healthy under 5 years old especially in developing countries. Although specific vaccines have preventive effects, antiviral therapy is essential for the diarrhea patients. Ziyuglycoside II is a traditional Chinese herb which has been proven to possess anti-virus effects. This study aimed to investigate the roles of Ziyuglycoside II in rotavirus-induced diarrhea and the underlying molecular mechanism. We found that normal MA104 cells treated with RV became swollen and gather together. However, Ziyuglycoside II treatment inhibited cell growth in a dose- and time dependent manner and suppressed RV replication. Moreover, Ziyuglycoside II reversed RV-induced downregulation of anti-inflammatory cytokine interleukin (IL)-10 and upregulation of pro-inflammatory factors, such as interferon-γ (IFN-γ), IL-1β, IL-6, and tumor necrosis factor (TNF-α). Moreover, Ziyuglycoside II administration and ribavirin blocked toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway both in mRNA and protein level, which was paralleled with immunohistochemical assay. Additionally, Ziyuglycoside II administration improved diarrhea symptoms and decreased diarrhea scores. Ziyuglycoside II and ribavirin inhibited the apoptosis of small intestine epithelial cells induced by RV. Taken together, RV treatment induced diarrhea. Ziyuglycoside II administration inhibited TLR4/NF-κB pathway and inflammatory response and improved RV-induced diarrhea. The inhibitory effects of Ziyuglycoside II on RV-induced diarrhea predicted Ziyuglycoside II may be a promising drug for diarrhea.

In this study, we investigated the physicochemical properties and composition of monosaccharidex from Polygonatum sibiricum. Simultaneously, we explored the in vivo and in vitro immunomodulatory activity and mechanism of Polygonatum sibiricum polysaccharide (PSP) activity by monitoring changes in immune organs, immune cells, and cytokines. The average molecular weight (M_w) of PSP was 9.514 × 10⁴ Da. The monosaccharide components of PSP were galactose, rhamnose, arabinose, mannose, and glucose at a molar ratio of 11.72 : 1.78 : 4.15 : 1.00 : 2.48. PSP increased thymus and spleen indices, enhance the proliferative responses of splenocytes, and increased the phagocytosis of mononuclear macrophages. Simultaneously, PSP could recover the body mass of immunosuppressed mice, and increased blood erythrocyte counts in the sera of cyclophosphamide (Cy)-treated and normal mice, whilst blood leukocytes and platelet counts of Cy-treated mice recovered. PSP elevated the CD4⁺/CD8⁺ ratio is a dose-dependent manner and increased the levels of interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) in the sera of Cy-treated mice. PSP further enhanced the expression of IL-2 and TNF-α in spleen lymphocytes. Additionally, PSP treatment accelerated the recovery of natural killer cell activity in a dose-dependent manner. Taken together, PSP not only regulated the immune function of normal mice, but participated in the protection against immunosuppression in Cy-treated mice, highlighting its potential as an immunostimulant.

The purpose of the present study was to investigate the protective effects and the underlying mechanisms of Danshensu on liver injury induced by iron overload. The mouse model was induced by injection of iron dextran intraperitoneally for 14 d. Danshensu significantly ameliorated liver injury by decreasing iron accumulation in the liver, possibly by down-regulating the expression of iron uptake-related proteins: divalent metal ion transporters-1 (DMT-1), transferrin receptor (TfR), and L-type calcium channel α1C subunit. Furthermore, Danshensu alleviated oxidative stress injury through potentiating glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities; Immunohistochemistry results demonstrated that Danshensu reduced the expression of inflammatory cytokines: interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β). Moreover, Danshensu prominently inhibited hepatocyte apoptosis through decreasing Bax and Caspase-3 and increasing Bcl-2 expression levels. The present results suggest that Danshensu possess significant hepatic-protection at least partly through inhibition of iron uptake, oxidative stress, inflammatory, and apoptosis. Therefore, we believe that Danshensu could be used as a promising therapeutic agent for preventing and treating iron overload diseases.

The interaction of human leukocyte antigen (HLA) with specific drugs is associated with delayed-type hypersensitivity reactions, which cause severe cutaneous toxicity. Such interactions induce structural alterations in HLA complexes via several different mechanisms such as the hapten theory, p-i concept, and altered peptide repertoire model, leading to the activation of cytotoxic T cells. To date, comprehensive detection of such structural alterations in preclinical studies has been difficult. Here, we evaluated structural alterations in HLA complexes focusing on the interaction between the HLA-B*57 : 01 allele and abacavir (an anti-human immunodeficiency virus drug), representing a model of abacavir hypersensitivity syndrome induced by changes in the peptide repertoire on the HLA molecule. We employed a phage display method using a commercially available antibody library to screen specific phage antibodies able to recognize HLA-B*57 : 01. The affinity of selected phage antibodies increased because of structural alterations in HLA-B*57 : 01 following exposure to abacavir, indicating that specific phage antibodies can identify drug-mediated structural changes in HLA complexes. We also identified an unreported structural change in HLA-B*57 : 01 using the phage display method, whereby abacavir increased the expression of peptide-deficient HLA-B*57 : 01 on the cell surface. These results suggest that phage display technology is a useful method for detecting structural changes in HLA complexes. This technology represents a potential novel strategy for predicting HLA-associated hypersensitivity reactions by drugs in pre-clinical studies.

Efficiency (speed and cost) and animal welfare are important factors in the development of new drugs. A novel method (the half-life method) was developed to predict the human plasma concentration–time profile of a monoclonal antibody (mAb) after intravenous (i.v.) administration using less data compared to the conventional approach; moreover, predicted results were comparable to conventional method. This new method use human geometric means of pharmacokinetics (PK) parameters and the non-human primates (NHP) half-life of each mAb. PK data on mAbs in humans and NHPs were collected from literature focusing on linear elimination, and the two-compartment model was used for analysis. The following features were revealed in humans: 1) the coefficient of variation in the distribution volume of the central compartment and at steady state of mAbs was small (22.6 and 23.8%, respectively) and 2) half-life at the elimination phase (t1/2_β) was the main contributor to plasma clearance. Moreover, distribution volume showed no significant correlation between humans and NHPs, and human t1/2_β showed a good correlation with allometrically scaled t1/2_β of NHP. Based on the features revealed in this study, we propose a new method for predicting the human plasma concentration–time profile of mAbs after i.v. dosing. When tested, this half-life method showed reasonable human prediction compared with a conventional empirical approach. The half-life method only requires t1/2_β to predict human PK, and is therefore able to improve animal welfare and potentially accelerate the drug development process.