Lead Optimization of Butyrolactone I as an Orally Bioavailable Antiallergic Agent Targeting FcγRIIB.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.

SERUM DISPOSITION OF A SINGLE DOSE OF ORALLY ADMINISTERED FIROCOXIB IN AFRICAN ELEPHANTS (LOXODONTA AFRICANA).

The time course of serum firocoxib concentrations was described after administration of two single oral doses (0.01 and 0.1 mg/kg) of commercially available firocoxib tablet (n = 4) and paste (n = 2) formulations to six healthy adult female African (Loxodonta africana) elephants. Firocoxib was quantitated by high-performance liquid chromatography. Firocoxib serum concentrations were below detectable levels after administration of 0.01 mg/kg of both formulations. A dose of 0.1 mg/kg (n = 4) of the tablet formulation had the following mean ± SD of pharmacokinetic parameters: area under the curve (AUC) 1,588 ± 362 h × ng/ml, maximum plasma concentration (Cmax) 31 ± 6.6 ng/ml at 6.4 ± 1.8 h, and disappearance half-life (T1/2) 66 ± 59 h, Elephant compliance to oral administration of the paste formulation was challenging, with only two elephants accepting administration of the paste at 0.1 mg/kg. Pharmacokinetic parameters determined included AUC of 814 h × ng/ml, Cmax of 44 ng/ml at Tmax of 7.0 h, and T1/2 of 36.4 h. Based on mean AUC, the relative bioavailability of paste compared to tablet formulations was 50%. Limitations of this study were the small number of participants and elephant compliance with the paste formulation. This study supports an oral dose of 0.1 mg/kg every 24 h. Multidose and IV trials are indicated to confirm firocoxib dosing requirements for African elephants.

Pharmacokinetics and Metabolism Study of Deep-Sea-Derived Butyrolactone I in Rats by UHPLC-MS/MS and UHPLC-Q-TOF-MS.

Butyrolactone I (BTL-I) is a butanolide isolated from the deep-sea-derived fungus, Aspergillus sp. It provides a potential new target for the prevention and treatment of food allergies. This study aimed to investigate the metabolic and pharmacokinetic profile of BTL-I in rats. The metabolic profiles were obtained by UHPLC-Q-TOF-MS. As a result, eleven metabolites were structurally identified, and the proposed metabolic pathways of BTL-I were characterized. The main metabolites were the oxidative and glucuronidative metabolites. In addition, a sensitive UHPLC-MS/MS method was established for the quantitation of BTL-I in rat plasma (LOQ = 2 ng/mL). The method was fully validated and successfully applied to the pharmacokinetic study of BTL-I in rats after oral administration or intravenous administration. The oral bioavailability was calculated as 6.29%, and the maximum plasma concentrations were 9.85 ± 1.54 ng/mL and 17.97 ± 1.36 ng/mL for intravenous and intragastric dosing groups, respectively.

Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration.

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (Tmax ) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.

Z-ligustilide: A review of its pharmacokinetics and pharmacology.

Z-ligustilide is a natural benzoquinone derivative found in many widely used Chinese herbal medicines such as Angelica sinensis (Oliv.) Diels as well as Ligusticum chuanxiong Hort and so on. It has been used as a part of traditional Chinese medicine and is also present in various Chinese medicine preparations. Pharmacokinetic studies have shown that Z-ligustilide has poor oral bioavailability in rats due to severe first-pass metabolic reactions. New evidence suggests that Z-ligustilide has a wide range of pharmacological properties, including anticancer, antiinflammatory, anti-oxidant as well as neuroprotective activities and so on. The literature discussed is derived from readily accessible papers spanning the early 1970s to the end of March 2019. Information were collected from journals, books, and online searches (Google Scholar, PubMed, Science Direct, Science Citation Index Finder, Springer link, and CNKI). This review intends to provide a comprehensive overview of the pharmacokinetics and pharmacology of Z-ligustilide in recent years, with a focus on its biological properties and mechanisms, which is of great significance for Chinese medicine.

Pharmacokinetics, tissue distribution, and safety evaluation of a ligustilide derivative (LIGc).

Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels and has a neuroprotective effect against ischemic stroke. However, owing to its multi-conjugated unstable structure, the compound has poor drug-forming properties. Therefore, we synthesized highly stable colorless needle crystals (known as ligusticum cycloprolactam, LIGc) through the structural modification of LIG. After a stability experiment was conducted at room temperature for four months, no impurity peaks were found by HPLC-DAD analysis, which indicated that LIGc resolved the stability issues of LIG. LIGc was absorbed and eliminated rapidly after intravenous administration (Cmax = 6.42 ±â€¯1.65 mg/L at a dose of 20 mg/kg) and oral administration (Tmax = 0.5 h, Cmax = 9.89 ±â€¯1.62 mg/L at a dose of 90 mg/kg, t1/2z approximately 2.5 h). The absolute oral bioavailability (F) of LIGc was clearly higher than the F of LIG reported in the literature (F, 83.97 % versus 2.6 %). Linear dose-dependent pharmacokinetics were observed after oral administration, with a higher area under the curve (AUC0-t, 22.31 ±â€¯2.88 mg/L*h) observed at 90 mg/kg than that at 45 mg/kg (AUC0-t, 13.673 ±â€¯0.666 mg/L*h). Tissue distribution results indicated that LIGc easily crossed the blood-brain barrier (BBB) and was distributed widely to the main tissues and organs of rats. We also conducted a preliminary safety assessment of LIGc by means of an acute toxicity test in KM mice. All mice had excellent health status (ig, dosage of 5.0 g/kg), with no histopathological changes observed in the main organs.

Pharmacokinetics and bioavailability of oral firocoxib in adult, mixed-breed goats.

Pharmacokinetic (PK) studies of oral firocoxib in large animal species have been limited to horses, preruminating calves, and adult camels. The aim of this study was to describe pharmacokinetics and bioavailability of firocoxib in adult goats. Ten healthy adult goats were administered 0.5 mg/kg firocoxib intravenously (i.v.) and per os (p.o.) in a randomized, crossover study. Plasma firocoxib concentrations were measured over a 96-hr period for each treatment using HPLC and mass spectrometry, and PK analysis was performed. The p.o. formulation reached mean peak plasma concentration of 139 ng/ml (range: 87-196 ng/ml) in 0.77 hr (0.25-2.00 hr), and half-life was 21.51 hr (10.21-48.32 hr). Mean bioavailability was 71% (51%-82%), indicative of adequate gastrointestinal absorption of firocoxib. There were no negative effects observed in any animal, and all blood work values remained within or very near reference range at the study's conclusion. Results indicate that oral firocoxib is well-absorbed and rapidly reaches peak plasma concentrations, although the concentration also decreased quickly prior to the terminal phase. The prolonged half-life may suggest tissue accumulation and higher plasma concentrations over time, depending on dosing schedule. Further studies to determine tissue residue depletion, pharmacodynamics, and therapeutic concentrations of firocoxib in goats are necessary.

Simultaneous quantification of ligustilide, dl-3-n-butylphthalide and senkyunolide A in rat plasma by GC-MS and its application to comparative pharmacokinetic studies of Rhizoma Chuanxiong extract alone and Baizhi Chuanxiong Decoction.

The herb couple has special clinical significance in reducing the toxicity and increasing the efficacy of drugs. The combination of Radix Angelicae Dahuricae (Baizhi, BZ) and Rhizoma Chuanxiong (ChuanXiong, CX) is a traditional herb couple. The combination performs better than the CX extract alone in the treatment of migraine and has been used for thousands of years. However, the specific compatibility mechanisms are still unclear. Ligustilide, dl-3-n-butylphthalide and senkyunolide A are the major active ingredients in CX and BZ-CX decoction. However, a comprehensive study of the pharmacokinetics of CX has not been carried out. A gas chromatography-mass spectroscopy (GC-MS) method with high selectivity, sensitivity and accuracy was developed. An SH-Rxi-5Sil (30 m × 0.25 mm i.d., and 0.25 µm film thickness) column was employed in the GC separation. Selectivity, linearity, precision, accuracy, recovery, matrix effect and stability were used to validate the current GC-MS method. Using the validated method, this is the first time to study on the comparative pharmacokinetics of ligustilide, dl-3-n-butylphthalide and senkyunolide A from CX alone and BZ-CX decoction in rat plasma. The pharmacokinetic parameters (Cmax , Tmax , T1/2 , AUC0-t , AUC0-∞ and CLz/F) of all of the detected ingredients showed significant differences between the two groups (P < 0.05). The results are helpful for further investigation of the compatibility mechanism of BZ-CX decoction.

Pharmacological Regulation in the USA and Pharmacokinetics Parameters of Firocoxib, a Highly Selective Cox-2, by Pain Management in Horses.

The objective of the study was to conduct a review of the pharmacological regulation and pharmacokinetic parameters of firocoxib when administered orally or intravenously in horses. A search for literature was done in SCOPUS and PubMed for studies that had to evaluate the pharmacological regulation as well as the pharmacokinetic parameters of firocoxib when administered in horses. The nonsteroidal anti-inflammatory drugs have analgesic, anti-inflammatory, antipyretics, and antiendotoxic effects. The newly developed is selective to COX2 characterized by less adverse effects in veterinary patients when administered at the recommended doses and do not exceed the established prescribed time. Firocoxib is authorized by the Food and Drug Administration for the treatment of pain in horses, whereas for humans, there is still no approval. Controversy has arisen because the administration of the same pharmaceutical presentation in horses and dogs has pharmacokinetic differences between animal species. However, special attention must be paid to pharmacokinetic differences between species like in horses and dogs. In the case of the horse, the dosage is 0.1 mg/kg in single dose or up to 14 days in oral paste formulation and can keep maintained on the same concentration for a period of 7-14 days in oral tablet formulation. Thorough knowledge of pharmacological regulations and pharmacokinetic parameters, it allows the posology and effective application of firocoxib in pathologies associated with chronic pain, avoiding the indiscriminate use by owners and in some cases veterinarians, thus reducing the negative impacts on horse's health.

Transmammary delivery of firocoxib to piglets reduces stress and improves average daily gain after castration, tail docking, and teeth clipping1.

Painful processing procedures in piglets such as tail docking, castration, and teeth clipping are an emerging animal welfare concern. We hypothesized that transmammary delivery of a nonsteroidal anti-inflammatory drug, firocoxib, would reduce pain associated with processing in piglets. This study compared the pharmacokinetics, efficacy, safety, and tissue residue concentrations of 4 doses of firocoxib (0.5, 1.0, 1.5, or 2.0 mg/kg) administered to sows and delivered to nursing piglets prior to processing. Sixteen sows, 5 ± 2 d postpartum, were randomly assigned to 1 of 4 treatment groups. On day 0, sows received a single intramuscular dose of firocoxib at 7 ± 1 h before piglet surgical castration, tail docking, and teeth clipping (males) or sham handling (females). Firocoxib and cortisol concentrations were determined from selected samples collected from sows and 3 piglets per litter (2 barrows and 1 gilt) at 0, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h after drug administration. On day 21, piglets were weighed and all animals were euthanized and necropsied. Tissues were collected from 3 piglets per litter for histological examination and drug residue analysis. Mean (±SEM) peak plasma firocoxib concentrations (Cmax) were 107.90 ± 15.18, 157.50 ± 24.91, 343.68 ± 78.89, and 452.83 ± 90.27 ng/mL in sows receiving 0.5, 1.0, 1.5, and 2.0 mg/kg firocoxib, respectively, and 9.53 ± 1.21, 31.04 ± 6.79, 53.30 ± 11.1, and 44.03 ± 7.47 ng/mL in their respective piglets. Mean plasma terminal half-life values ranged from 26 to 31 h in sows and 30 to 48 h in piglets. Barrows nursing sows that received 2.0 mg/kg firocoxib had a lower mean plasma cortisol concentration at 1 ± 1 h after processing compared with barrows nursing sows that received 1.0 mg/kg (P = 0.0416) and 0.5 mg/kg of firocoxib (P = 0.0397). From processing to weaning, litters of sows receiving 2.0 mg/kg firocoxib gained more weight than litters of sows that received 0.5 mg/kg (P = 0.008) or 1.0 mg/kg (P = 0.005). No signs of nonsteroidal anti-inflammatory drug toxicity were observed on examination of the kidney, liver, stomach, and small intestine, and concentrations of firocoxib and the descyclopropylmethyl metabolite were below the limit of detection (0.01 µg/g) in all tissues examined from sows and piglets. These findings indicate that maternal delivery of firocoxib to suckling piglets before tail docking and castration may safely reduce processing-induced stress and enhance production by increasing weaning weights.

Anticancer and antimetastatic potential of enterolactone: Clinical, preclinical and mechanistic perspectives.

Currently cancer is the second leading cause of death globally and worldwide incidence and mortality rates of all cancers of males and females are rising tremendously. In spite of advances in chemotherapy and radiation, metastasis and recurrence are considered as the major causes of cancer related deaths. Hence there is a mounting need to develop new therapeutic modalities to treat metastasis and recurrence in cancers. A significant amount of substantiation from epidemiological, clinical and laboratory research highlights the importance of diet and nutrition in cancer chemoprevention. Enterolactone (EL) is a bioactive phenolic metabolite known as a mammalian lignan derived from dietary lignans. Here in we review the reported anti-cancer properties of EL at preclinical as well as clinical level. Several in-vivo and in-vitro studies have provided strong evidence that EL exhibits potent anti-cancer and/or protective properties against different cancers including breast, prostate, colo-rectal, lung, ovarian, endometrial, cervical cancers and hepatocellular carcinoma. Reported laboratory studies indicate a clear role for EL in preventing cancer progression at various stages including cancer cell proliferation, survival, angiogenesis, inflammation and metastasis. In clinical settings, EL has been reported to reduce risk, decrease mortality rate and improve overall survival particularly in breast, prostate, colon, gastric and lung cancer. Further, the in-vitro human cell culture studies provide strong evidence of the anticancer and antimetastatic mechanisms of EL in several cancers. This comprehensive review supports an idea of projecting EL as a promising candidate for developing anticancer drug or adjunct dietary supplements and nutraceuticals.

Kinsenoside: A Promising Bioactive Compound from Anoectochilus Species.

Kinsenoside is a main active component isolated from plants of the genus Anoectochilus, and exhibits many biological activities and pharmacological effects, including hepatoprotective, anti-hyperglycemic, anti-hyperliposis, anti-inflammatory, vascular protective and anti-osteoporosis effects and so on, which is contributing to its promising potency in disease treatments. This review aims to recapitulate the pharmacological functions of kinsenoside, as well as its source, extraction, identification, quantitative analysis, pharmacokinetics, synthesis and patent information. The data reported in this work can confirm the therapeutic potential of kinsenoside and provide useful information for further new drug development.

Self-nanoemulsifying drug-delivery systems improve oral absorption and antischistosomal activity of epiisopiloturine.

AIM: To develop a self-nanoemulsifying drug-delivery system (SNEDDS) able to improve oral absorption of epiisopiloturine (EPI), and test the antischistosomal activity in a mice model. RESULTS: SNEDDS had a nanoscopic size and was able to enhance EPI bioavailability after oral administration, and SNEDDS-EPI (40 mg.kg-1) improved the in vivo antischistosomal activity of EPI, demonstrating that SNEDDS was able to improve the pharmacokinetics of EPI, and to maintain the pharmacodynamic activity against Schistosoma mansoni in vivo. CONCLUSION: Taken together, these results indicate that SNEDDS-EPI is efficient in reducing worm burden in comparison to treatment with the free version of EPI. [Formula: see text].

Deaths in the Lesbian, Gay, Bisexual and Transgender United Kingdom Communities Associated with GHB and Precursors.

BACKGROUND: Misuse of gammahydroxybutrate (GHB) and its prodrugs gammabutyrolactone (GBL) and 1,4 butanediol (1,4-BD) has increased greatly since the early 1990s, particularly amongst lesbian, gay, bisexual and transgender (LGBT) individuals in recreational and sexual settings, e.g. 'chemsex'. OBJECTIVE AND METHOD: This paper presents an overview of GHB pharmacotoxicology and provides analyses of cases in the LGBT population associated with the use of these substances extracted from the UK's National Programme on Substance Abuse Deaths database, to which notification is voluntary. RESULTS: From 1995 to September 2013, 21 GHB/GBL-associated fatalities were reported. None involved 1,4-BD. Typical victims were: Male (100%); White (67%), young (mean age 34 years); employed (90%); with a drug misuse history (81%). Most deaths were accidental (67%) or related to recreational drug use (19%), the remaining (potential) suicides. The majority of fatalities (83%) occurred in private residences, typically following recreational use; others occurred in specific 'gay'-oriented locales including clubs and saunas. Three London boroughs accounted for 62% of all notified deaths, reflecting the concentration of both resident and visiting 'gay' individuals. However, this may be an artefact of the voluntary nature of the data submission procedure in particular areas. GHB/GBL alone was implicated in 10% of fatalities. The following substances were implicated either alone or in combination in the remaining cases (percentages may add to more than 100%): cocaine (38%); alcohol (33%); amphetamines (29%); ecstasy (29%); diazepam (24%); ketamine (24%); mephedrone (24%). Post-mortem blood levels: mean 660 (range 22 - 2335; S.D. 726) mg/L. CONCLUSION: Significant caution is needed when ingesting GHB/GBL, particularly with alcohol, benzodiazepines, stimulants, and ketamine. Risk of death is increased due to their CNS-depressant properties. Of these, 'chemsex' drugs such as cocaine, mephedrone and ketamine are of note. More awareness is needed in the 'gay' community about risks associated with the consumption of such substances.

Short communication: The mammalian lignan enterolactone is absorbed by newborn dairy calves fed enterolactone-enriched milk.

Flaxseed is the richest source of the plant lignan secoisolariciresinol diglucoside, which is converted to the mammalian lignans enterolactone (EL) and enterodiol by the gut microbiota of ruminants and humans. Enterolactone has been associated with improved animal and human health due to its antioxidant and anticarcinogenic properties. The objective of this study was to determine the pharmacokinetics of EL in newborn dairy calves fed milk replacer or EL-enriched milk. We hypothesized that newborn Holstein calves fed EL-enriched milk would have greater area under the curve and plasma concentration of EL compared with those fed milk replacer. On d 5 of life, calves were administered 2 L of milk replacer (n = 10; low-EL treatment: 123 nmol/L of EL) or 2 L of EL-enriched milk (n = 10; high-EL treatment: 481 nmol/L of EL) during the morning feeding (0700 h). Blood samples were taken from the jugular vein before (0 h) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, and 48 h after oral administration of treatments. The area under the curve for the plasma concentration of EL was analyzed according to the trapezoidal rule between 0 and 12 h after treatment administration, and it was greater in high- (26 nmol/L × h) than low-EL calves (4.30 nmol/L × h). Similarly, the maximum concentration of EL in plasma was greater in high- (5.06 nmol/L) versus low-EL calves (1.95 nmol/L). Furthermore, the time after treatment intake to reach maximum plasma concentration of EL was faster in high- (4.31 h) compared with low-EL (4.44 h) treatment. Calves were able to absorb EL, indicating that EL-enriched milk can potentially be used as source of EL to pre-weaned ruminants.

Pharmacokinetics of firocoxib after intravenous administration of multiple consecutive doses in neonatal foals.

The purpose of this study was to determine the pharmacokinetic profile of intravenous firocoxib in neonatal foals. Six healthy foals were administered 0.09 mg/kg firocoxib intravenously once a day for 7 days. Blood was collected for plasma firocoxib analysis using high-performance liquid chromatography with fluorescence detection at times 0 (day 1 of study only) and 0.08, 0.25, 1, 2, 4, 6, 8, 16 and 24 hr on dose numbers 1, 5 and 7. Blood was also collected immediately prior to doses 3, 4, 5 and 7. Final samples were collected at 36, 48, 72 and 96 hr following the final dose. Noncompartmental analysis using the trapezoidal method with linear interpolation revealed a moderate half-life (15.9 ± 9.1 hr) with a large volume of distribution at steady state (1.79 ± 0.57 L/kg) and a clearance (96.0 ± 59.2 ml h-1  kg-1 ) that was more rapid than that observed in adult horses.

Development of a hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the determination of kinsenoside, an antihyperlipidemic candidate, in rat plasma and its application to pharmacokinetic studies.

Kinsenoside is a major bioactive constituent isolated from Anoectochilus formosanus and is investigated as an antihyperlipidemic candidate. In this study, a rapid, sensitive, and reliable bioanalytical method was developed for the determination of kinsenoside in rat plasma using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The plasma sample was pretreated with 1% acetic acid, followed by protein precipitation with acetonitrile:methanol (70:30). Chromatographic separation was performed on a HILIC silica column (2.1mm×100mm, 3µm). The mobile phases consisted of 0.1% acetic acid in distilled water (solvent A) and 0.1% acetic acid in acetonitrile (solvent B). A gradient program was used at a flow rate of 0.2mL/min. For mass spectrometric detection, the multiple reaction monitoring mode was used; the MRM transitions were m/z 265.2→m/z 102.9 for kinsenoside and m/z 163.3→m/z 132.1 for the internal standard (IS) nicotine in the positive ionization mode. A calibration curve was constructed in the range of 2-500ng/mL. The intra- and interday precision and accuracy were within 5%. The HILIC-MS/MS method was specific, accurate, and reproducible and was successfully applied in a pharmacokinetic study of kinsenoside in rats.

Disposition of firocoxib in late pregnant and early postpartum mares.

Pregnancy induces several physiologic changes that might impact the bioavailability, distribution, metabolism, and excretion of drugs. The objective of this study was to determine the effects of pregnancy on the disposition of oral firocoxib in mares. Seven pony mares received oral firocoxib paste at a dose of 0.1 mg/kg during late pregnancy and again 12 to 33 days postpartum. Firocoxib concentrations were measured in plasma by HPLC with ultraviolet detection. Maximum plasma concentrations were significantly lower in pregnant (50.0 ± 21.8 ng/mL) than in postpartum (73.7 ± 25.6 ng/mL) mares. Plasma concentrations 24 h after administration, time to maximum plasma concentrations, and area under the plasma concentration versus time curve were not significantly different between late pregnancy and the postpartum period in mares.

Uptake and translocation of imidacloprid, clothianidin and flupyradifurone in seed-treated soybeans.

BACKGROUND: Seed treatment insecticides have become a popular management option for early-season insect control. This study investigated the total uptake and translocation of seed-applied [(14) C]imidacloprid, [(14) C]clothianidin and [(14) C]flupyradifurone into different plant parts in three soybean vegetative stages (VC, V1 and V2). The effects of soil moisture stress on insecticide uptake and translocation were also assessed among treatments. We hypothesized that (1) uptake and translocation would be different among the insecticides owing to differences in water solubility, and (2) moisture stress would increase insecticide uptake and translocation. RESULTS: Uptake and translocation did not follow a clear trend in the three vegetative stages. Initially, flupyradifurone uptake was greater than clothianidin uptake in VC soybeans. In V1 soybeans, differences in uptake among the three insecticides were not apparent and unaffected by soil moisture stress. Clothianidin was negatively affected by soil moisture stress in V2 soybeans, while imidacloprid and flupyradifurone were unaffected. Specifically, soil moisture stress had a positive effect on the distribution of flupyradifurone in leaves. This was not observed with the neonicotinoids. CONCLUSIONS: This study enhances our understanding of the uptake and distribution of insecticides used as seed treatments in soybean. The uptake and translocation of these insecticides differed in response to soil moisture stress. © 2015 Society of Chemical Industry.