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1.
Lab Anim ; 46(2): 108-13, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22238291

ABSTRACT

Gabapentin has been used to treat a variety of conditions in both human and veterinary medicine, including seizures, neuropathies and chronic pain. However, little information is known about the effects of gabapentin on the minimum alveolar concentration (MAC) of volatile anaesthetics. In this study, we investigated the effect of intraperitoneal administration of gabapentin on isoflurane MAC in adult male rats and hypothesized that gabapentin would decrease MAC in a dose-dependent manner. Using a standard MAC study protocol, we compared five treatment groups (G) receiving 0 (G(0)), 30 (G(30)), 100 (G(100)), 300 (G(300)) and 1000 (G(1000)) mg/kg gabapentin intraperitoneally and compared post-drug MAC values among groups and with corresponding baseline MAC values determined in each group prior to drug testing. The average baseline isoflurane MAC value was 1.45 ± 0.17%, which did not differ significantly between groups (1.47 ± 0.23% [G(30)], 1.46 ± 0.23% [G(100)], 1.48 ± 0.18% [G(300)] and 1.42 ± 0.2% [G(1000)]). In the G(300) and G(1000) groups, the isoflurane MAC value decreased significantly by 19% and 18%, respectively, from corresponding baseline values (P< 0.05, when compared with G(0)). Linear regression analysis revealed a negative correlation between blood gabapentin concentration and percent change in MAC (R(2) = 0.43; P< 0.05) but not dose. In conclusion, high-dose intraperitoneal gabapentin decreased isoflurane MAC. However, the effect was small and not dose-dependent, and is unlikely to be clinically significant.


Subject(s)
Amines/pharmacology , Anesthetics, Inhalation/pharmacokinetics , Anticonvulsants/pharmacology , Cyclohexanecarboxylic Acids/pharmacology , Isoflurane/pharmacokinetics , Pulmonary Alveoli/drug effects , gamma-Aminobutyric Acid/pharmacology , Anesthesia, Inhalation , Anesthetics, Inhalation/administration & dosage , Animals , Dose-Response Relationship, Drug , Gabapentin , Injections, Intraperitoneal , Isoflurane/administration & dosage , Male , Pulmonary Alveoli/metabolism , Rats , Rats, Sprague-Dawley
2.
Equine Vet J ; 36(5): 426-30, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15253084

ABSTRACT

REASONS FOR PERFORMING STUDY: Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. OBJECTIVES: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. METHODS: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with fasting. RESULTS: Dexamethasone i.v. caused significant improvement in lung function within 2 h with a peak effect at 4-6 h. Dexamethasone per os was effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior to feeding. The duration of effect was, for all dexamethasone treatments, statistically significant for 30 h when compared to saline and tended to have a longer duration of effect when used orally. Dexamethasone per os at a dose of 0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding decreases bioavailability. CONCLUSIONS: Dexamethasone administered i.v. has a rapid onset of action in RAO-affected horses. Oral administration of a bioequivalent dose of the same solution to fasted horses is as effective as i.v. administration and tends to have longer duration of action. Fasting horses before oral administration of dexamethasone improves the efficacy of treatment. POTENTIAL RELEVANCE: Oral administration to fasted horses of a dexamethasone solution intended for i.v. use provides an effective treatment for RAO-affected animals.


Subject(s)
Airway Obstruction/veterinary , Dexamethasone/therapeutic use , Horse Diseases/drug therapy , Administration, Oral , Airway Obstruction/drug therapy , Animals , Biological Availability , Cross-Over Studies , Dexamethasone/administration & dosage , Dexamethasone/pharmacokinetics , Dose-Response Relationship, Drug , Fasting/physiology , Female , Horses , Injections, Intravenous/veterinary , Male , Random Allocation , Recurrence , Treatment Outcome
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