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Pharmacokinetic profiles of 5 mg/kg ibudilast, a phosphodiesterase inhibitor, orally administered to dogs in fasted and non-fasted states. A preliminary study

Polish journal of veterinary sciences, 2018-06, Vol.21 (2), p.281-285 [Peer Reviewed Journal]

Copyright© by the Polish Academy of Sciences. ;Copyright Polish Academy of Sciences, Committee of Veterinary Sciences 2018 ;ISSN: 1505-1773 ;EISSN: 2300-2557 ;DOI: 10.24425/119049 ;PMID: 30450866

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Title:
Pharmacokinetic profiles of 5 mg/kg ibudilast, a phosphodiesterase inhibitor, orally administered to dogs in fasted and non-fasted states. A preliminary study
Author: Łebkowska-Wieruszewska, B ; De Vito, V ; Kowalski, C J ; Owen, H ; Poapolathep, A ; Lisowski, A ; Giorgi, M
Subjects: 3',5'-Cyclic-nucleotide phosphodiesterase ; Administration, Oral ; Allergies ; Analgesics ; Animals ; Area Under Curve ; Asthma ; Cerebrovascular diseases ; Cross-Over Studies ; Crossovers ; Dogs ; Drug dosages ; Experiments ; Fasting ; Food-Drug Interactions ; Narcotics ; Neuropathy ; Oral administration ; Pain ; Pharmacology ; Phosphodiesterase ; Phosphodiesterase inhibitors ; Phosphodiesterase Inhibitors - pharmacokinetics ; Pyridines - pharmacokinetics ; Statistical analysis
Is Part Of: Polish journal of veterinary sciences, 2018-06, Vol.21 (2), p.281-285
Description: Ibudilast (AV-411) is a non-selective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is currently marketed for human use in Asian countries for the treatment of asthma, cerebrovascular disorders and ocular allergies. Ibudilast has also been found to have an analgesic action for neuropathic pain at doses 5-10 times higher than those used in asthma therapy. Six healthy Labrador dogs were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, cross-over design (2x2 Latin-square). Dogs in group 1 (n=3) were fasted for at least 10 hours overnight before the beginning of the experiment and 4 h following dosing while dogs in group 2 (n=3) received food ad libitum. During the first phase, each dog in group 1 and 2 received a single dose of 5 mg/kg ibudilast administered orally. After 1-week washout period the groups were rotated and the experiment was repeated. The analytical method, validated for dog plasma, was shown to be linear in the range 0.10-20 μg/mL. The limit of detection (LOD) and quantification (LOQ) were 0.03 and 0.1 μg/mL, respectively. No behavioural or health alterations were observed in the animals during or after the study. Ibudilast was detectable in plasma for up to 24 h showing a wide variability between animals. Although no statistically significant differences were observed in the present study between the fed and fasted states, examination of the raw data suggests that an effect may be present. The wide degree of variation observed in area under the curve (AUC) suggests that the investigation of population pharmacokinetic modelling is warranted.
Publisher: Germany: Polish Academy of Sciences, Committee of Veterinary Sciences
Language: English;Polish
Identifier: ISSN: 1505-1773
EISSN: 2300-2557
DOI: 10.24425/119049
PMID: 30450866
Source: MEDLINE
ProQuest Central

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Pharmacokinetic profiles of 5 mg/kg ibudilast, a phosphodiesterase inhibitor, orally administered to dogs in fasted and non-fasted states. A preliminary study

Copyright© by the Polish Academy of Sciences. ;Copyright Polish Academy of Sciences, Committee of Veterinary Sciences 2018 ;ISSN: 1505-1773 ;EISSN: 2300-2557 ;DOI: 10.24425/119049 ;PMID: 30450866

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