Florfenicol is a fluorinated analog of thiamphenicol and has been used for treatment of animal respiratory infectious diseases with a mechanism of action of inhibiting protein synthesis of bacterial peptidyl transferase specifically on 70 S ribosomes (Cannon et al., 1990;Varma et al., 1991;Ueda et al., 1995). With modifications based on the chemical structure of chloramphenicol, florfenicol has been shown to not only circumvent the bacterial acetyltransferase-mediated drug resistance but also to ameliorate the risk of inducing drug-related aplastic anemia in humans (Syriopoulou et al., 1981;Soback et al., 1995).Pharmacokinetics of florfenicol have been described in calves, cows, broiler chickens and muscovite ducks (Varma et al., 1986;Bretzlaff et al., 1987;Lobell et al., 1994;Soback et al., 1995;el-Banna, 1998;Shen et al., 2003). Recently, florfenicol tends to be increasingly used for treating porcine pneumonias caused by Actinobacillus pleuropneumoniae (Ueda et al., 1995;Liu et al., 2003) and Pasteurella multocida (Voorspoels et al., 1999). We wished to evaluate pharmacokinetics of florfenicol in pigs following intravenous (i.v.), intramuscular (i.m.) or oral (p.o.) administration and the potential feed-effect on its oral dosing.Twelve clinically-healthy crossbred pigs (Duroc · Landrace · Yorkshire) were housed in semi-contained pens with access to water ad libitum and a commercial nonmedicated chow at scheduled times. Pharmacokinetics of florfenicol was first studied in six animals (b.w., 24.7 ± 1.0 kg), which were divided into three groups according to the Latin square design. Each group of two animals received a single dose of florfenicol at 20 mg/kg via i.v., i.m. or p.o. administration sequentially, with a 10-day washout between treatments. An injection solution of florfenicol (300 mg/mL; Huihua, Guangzhou, China) was given i.v. via the ear vein or i.m. An amylum-based powder containing 15% florfenicol (Huihua) was given orally by gavage. Blood samples of each 5 mL were collected prior to the i.v. dosing and at 0.083, 0.167, 0.25, 0.5, 0.75, 1,, 1.5, 2, 3, 4, 6, 9, 12, 15, 24, 36 and 48 h thereafter; to the i.m. dosing and at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 15, 24, 36 and 48 h thereafter; to the p.o. doing and at 0.083, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9, 12, 15, 24, 36 and 48 h thereafter, respectively. Plasma was prepared immediately and stored at )20°C until analysis.The effect of feed intake on the pharmacokinetics of florfenicol was next studied in six pigs (b.w., 15.3 ± 1.2 kg). Two groups of three animals were designated to undergo either fasting for 16 h or feeding for 1 h with the standard diet before they were orally given a single dose of florfenicol at 20 mg/kg. Blood samples were taken immediately prior to the drug treatment and at 0. 083, 0.5, 0.75,1, 2, 3, 4, 9, 12, 15, 24, 36 and 48 h thereafter, followed by the immediate preparation of plasma. After a 10-day washout, animals were crossover to the alternative condition followed a repetition of the above pharmacokinetic study....

The maleate salt-based tablet formulations were bioequivalent to the diHCl tablet formulation. The extent of the observed effect of a high-fat, high-calorie meal or concurrent rabeprazole treatment on glasdegib exposure is not considered clinically meaningful.

A topical application of 12-0-tetradecanoylphorbol-13-acetate (TPA) to mouse ear surface induces nonallergic inflammation, i.e. ear edema. Oral administration of 3-30 mg/kg of l-{[5’-(3”-methoxy-4”-ethoxycarbonyloxyphenyl)-2’,4’-pentadienoyl]aminoethyl}-4-diphenylmethoxypiperidine (TMK 688), a potent 5-lipoxygenase inhibitor with antihistamine activity, inhibited TPA-induced ear edema in a dose-dependent manner. TMK688 inhibited not only 5-lipoxygenase activity but also epidermal cyclooxygenase activity. 1 – {[ 5 ‘ (3 “ methoxy – 4”-hy droxyphenyl) – 2’, 4’- pentadienoyl] -aminoethyl}-4-diphenylmethoxypiperidine (TMK777), an active metabolite of TMK688, had more potent 5-lipoxygenase inhibitory activity but less potent cyclooxygenase inhibitory activity than TMK688. Oral administration of TMK688 (30 mg/kg) markedly inhibited TPA-stimulated LTB₄ formation in mouse skin but TPA-stimulated PGE₂ formation only slightly. Our experimental results suggest that both cyclooxygenase inhibitory activity and antihistamine activity of TMK688 are not essential to its anti-inflammatory action. The anti-inflammatory effect of orally administered TMK688 is due most probably to the anti-5-lipoxygenase activity of TMK688 and its active metabolite TMK777.

No abstract