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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Ibudilast is an oral drug approved in Asia for asthma.• Tolerability of 10-mg regimens has been described previously.• Published pharmacokinetics (PK) are limited: single or 7-day repeat oral administration of 10 mg in healthy male Asian volunteers. WHAT THIS STUDY ADDS• Safety/tolerability and PK of a single 30-mg dose and a 30-mg twice daily (b.i.d.) 2-week regimen in male and female healthy volunteers. • Higher-dose regimens are relevant for testing in new neurological indications.• LC-MS/MS analytics for quantification of plasma and urine levels of ibudilast parent and its primary metabolite (6,7-dihydrodiol-ibudilast). AIMSTo investigate the safety, tolerability and pharmacokinetics (PK) of ibudilast after a single-dose and a multiple-dose regimen. METHODSHealthy adult male (n = 9) and female (n = 9) volunteers were evaluated over a 17-day stay in a Phase 1 unit. Subjects were randomized 1 : 3 to either oral placebo or ibudilast at 30-mg single administration followed by 14 days of 30 mg b.i.d. Complete safety analyses were performed and, for PK, plasma and urine samples were analysed for ibudilast and its major metabolite. RESULTSIbudilast was generally well tolerated. No serious adverse events occurred. Treatment-related adverse events included hyperhidrosis, headache and nausea. Two subjects discontinued after a few days at 30 mg b.i.d. because of vomiting. Although samples sizes were too small to rule out a sex difference, PK were similar in men and women. The mean half-life for ibudilast was 19 h and median Tmax was 4-6 h. Mean (SD) steady-state plasma Cmax and AUC0-24 were 60 (25) ng ml -1 and 1004 (303) ng h ml -1 , respectively. Plasma levels of 6,7-dihydrodiol-ibudilast were approximately 30% of the parent. CONCLUSIONSIbudilast is generally well tolerated in healthy adults when given as a single oral dose of 30 mg followed by 30 mg b.i.d. (60 mg day -1 ) for 14 days. Plasma PK reached steady state within 2 days of starting the b.i.d. regimen. Exposure to ibudilast was achieved of a magnitude comparable to that associated with efficacy in rat chronic pain models.

The objective of this study was to investigate the pharmacokinetics and bioavailability of valnemulin in broiler chickens after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 10 mg/kg body weight (bw). Plasma samples were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic characterization was performed by non-compartmental analysis using WinNonlin program. After intravenous administration, distribution was wide with the volume of distribution based on terminal phase(V(z)) of 4.27 ± 0.99 L /kg. Mean valnemulin t(1/2β)(h), Cl(β)(L /h /kg), V(ss)(L /kg) and AUC((0-∞))(μg·h /mL) values were 2.85, 0.99, 2.72 and 10.34, respectively. After intramuscular administration, valnemulin was rapidly absorbed with a C(max) of 2.2 μg/mL achieved at 0.43 h (t(max)), and the absolute bioavailability (F) was 88.81%; and for the oral route the same parameters were 0.66 ± 0.15 μg/mL, 1.54 ± 0.27 h and 74.42%. A multiple-peak phenomenon was present after oral administration. The plasma profile of valnemulin exhibited a secondary peak during 2-6 h and a tertiary peak at 32 h. The favorable PK behavior, such as the wide distribution, slow elimination and acceptable bioavailability indicated that it is likely to be effective in chickens.

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Objectives Chamomile has long been used as a medicinal plant due to its antioxidative and anti-inflammatory activity. Apigenin-7-O-glucoside (AG) is one of the major ethanol extract components from chamomile; however, the underlying mechanism remains unclear. Methods In this study, the antioxidant potential and the anti-inflammatory activities of AG were analysed and compared with those of trolox. We demonstrate the protective effects of AG on free radical-induced oxidative damage of DNA, proteins and erythrocytes. Flow cytometry assay was used to detect ROS production. Additionally, the expression of anti-oxidation-related and inflammation-related factors was detected by ELISA and Western blotting, respectively. Key findings AG and trolox showed different efficiency as antioxidant in different experimental systems. AG had similar effect as trolox to inhibit H 2 O 2-induced ROS production in RAW264.7 cells, while exerted stronger inhibition against free radical-induced oxidative damage on erythrocytes than trolox. Interestingly, compared with trolox, AG also had stronger inhibitory effect on LPS-induced NF-κB/NLRP3/caspase-1 signalling in RAW246.7 cells. Conclusions These results suggest the potential of AG as a pharmaceutical drug for anti-oxidation and anti-inflammation, and the combined usage of AG and trolox might promote its efficacy. Our findings will provide new insights into the development of new drugs with antioxidative and anti-inflammatory functions.