RESUMO
Dexmedetomidine, the most selective α2-adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 µg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance from the lower lip of the horse to the ground measured in centimetre. The harmonic mean (SD) plasma elimination half-life (Lambda z half-life) for dexmedetomidine was 20.9 (5.1) min, clearance (Cl) was 0.3 (0.20) L/min/kg, and volume of distribution at steady-state (Vdss ) was 13.7 (7.9) L/kg. There was a considerable individual variation in the concentration of dexmedetomidine vs. time profile. The level of sedation covaried with the plasma concentration of dexmedetomidine. This implies that for clinical use of dexmedetomidine constant rate infusion in conscious horses, infusion rates can be easily adjusted to effect, and this is preferable to an infusion at a predetermined value.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Dexmedetomidina/farmacocinética , Cavalos/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Animais , Área Sob a Curva , Dexmedetomidina/administração & dosagem , Esquema de Medicação , Feminino , Meia-Vida , Cavalos/sangue , MasculinoRESUMO
The pharmacokinetics and the analgesic, anti-inflammatory and antipyretic effects of meloxicam were investigated in a placebo controlled study in 2-week-old piglets. Inflammation was induced by a subcutaneous injection of kaolin in the left metacarpus, and 16 h later, meloxicam (0.6 mg/kg) or saline was administered intramuscularly. The absorption half-life was relatively short (0.19 h) and the elimination half-life was 2.6 h. Mechanical nociceptive threshold testing was used to evaluate the analgesic effect, but no significant effect of the meloxicam treatment was found. The skin temperature of the inflamed area increased after the kaolin injection, but no significant decrease in temperature was found after administration of meloxicam. Only limited pyresis was observed after the kaolin injection, and no significant antipyretic effect of meloxicam was found. The results indicated that this dose of meloxicam had very limited anti-inflammatory and analgesic effects in piglets.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Inflamação/veterinária , Doenças dos Suínos/tratamento farmacológico , Suínos/metabolismo , Tiazinas/farmacocinética , Tiazóis/farmacocinética , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/uso terapêutico , Temperatura Corporal , Cromatografia Líquida/veterinária , Esquema de Medicação/veterinária , Feminino , Febre/induzido quimicamente , Febre/tratamento farmacológico , Febre/veterinária , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Injeções Intramusculares/veterinária , Caulim , Masculino , Meloxicam , Medição da Dor/veterinária , Doenças dos Suínos/induzido quimicamente , Espectrometria de Massas em Tandem/veterinária , Tiazinas/sangue , Tiazinas/uso terapêutico , Tiazóis/sangue , Tiazóis/uso terapêuticoRESUMO
Following intravenous dose of 6mg/kg racemic ketoprofen, the chiral pharmacokinetics of ketoprofen was investigated in eight piglets aged 6 and 21days old. S-ketoprofen predominated over R-ketoprofen in plasma of the piglets in both age groups. The volumes of distribution of S-ketoprofen for the 6- and 21-day-old piglets were 241.7 (211.3-276.5) mL/kg and 155.0 (138.7-173.1) mL/kg, respectively, while the corresponding parameters for R-ketoprofen were 289.2 (250.3-334.2) mL/kg and 193.0 (168.7-220.8) mL/kg. The clearances of R-ketoprofen [948.4 (768.0-1171.2) mL/h/kg and 425 (319.1-566.0) mL/h/kg for the 6- and 21-day-old piglets, respectively] were significantly higher compared to the clearances of S-ketoprofen [57.3 (46.6-70.4) mL/h/kg and 33.8 (27.0-42.2) mL/h/kg for 6- and 21-day-old piglets, respectively]. The elimination half-life of S-ketoprofen was 3.4h for both age groups, while the elimination half-life of R-ketoprofen was 0.2h for the 6-day-old and 0.4h for the 21-day-old piglets. The clearances of both R- and S-ketoprofen were significantly higher in the 6-day-old piglets compared to when they were 21 days old. Furthermore, the volumes of distribution were larger in the youngest age group.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Cetoprofeno/farmacocinética , Suínos/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos/metabolismo , Anti-Inflamatórios não Esteroides/química , Área Sob a Curva , Feminino , Meia-Vida , Injeções Intravenosas/veterinária , Cetoprofeno/química , Masculino , Relação Estrutura-AtividadeRESUMO
The chiral pharmacokinetics and pharmacodynamics of ketoprofen were investigated in a placebo-controlled study in piglets after intramuscular administration of 6 mg/kg racemic ketoprofen. The absorption half-lives of both enantiomers were short, and S-ketoprofen predominated over R-ketoprofen in plasma. A kaolin-induced inflammation model was used to evaluate the anti-inflammatory, antipyretic and analgesic effects of ketoprofen. Skin temperatures increased after the kaolin injection, but the effect of ketoprofen was small. No significant antipyretic effects could be detected, but body temperatures tended to be lower in the ketoprofen-treated piglets. Mechanical nociceptive threshold testing was used to evaluate the analgesic effects. The piglets in the ketoprofen-treated group had significantly higher mechanical nociceptive thresholds compared to the piglets in the placebo group for 12-24 h following the treatment. Pharmacokinetic/pharmacodynamic modelling of the results from the mechanical nociceptive threshold testing gave a median IC(50) for S-ketoprofen of 26.7 µg/mL and an IC(50) for R-ketoprofen of 1.6 µg/mL. This indicates that R-ketoprofen is a more potent analgesic than S-ketoprofen in piglets. Estimated ED(50) for racemic ketoprofen was 2.5 mg/kg.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Febre/veterinária , Inflamação/veterinária , Cetoprofeno/farmacocinética , Doenças dos Suínos/metabolismo , Suínos/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Temperatura Corporal , Feminino , Febre/induzido quimicamente , Febre/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Caulim , Cetoprofeno/química , Cetoprofeno/uso terapêutico , Masculino , Modelos Biológicos , Dor/tratamento farmacológico , Dor/veterinária , Medição da Dor/veterinária , Doenças dos Suínos/induzido quimicamente , Doenças dos Suínos/tratamento farmacológicoRESUMO
The pharmacokinetics and pharmacodynamics of meloxicam in piglets (16-23 days old) were studied using a stratified parallel group design. One group (n = 13) received 0.4 mg/kg meloxicam intravenously, while the other group (n = 12) received physiological saline solution. A carrageenan-sponge model of acute inflammation was used to evaluate the effects of meloxicam. The plasma clearance was low (0.061 L/kg/h), the volume of distribution was low (0.19 L/kg) and the elimination half-life was short (2.7 h). At most time points, the mean concentration of meloxicam in plasma exceeded the concentrations in exudate indicating a limited accumulation of the drug at the site of the inflammation. There were significant differences between the groups in the exudate prostaglandin E2 (PGE2) concentration, but the inhibition of PGE2 in the meloxicam group was limited. The inhibition of thromboxane B(2) (TXB2) production in serum in the meloxicam group was extensive, but of shorter duration than the PGE2 inhibition in exudate.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Tiazinas/farmacocinética , Tiazóis/farmacocinética , Tromboxano A2/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Anti-Inflamatórios não Esteroides/farmacologia , Área Sob a Curva , Dinoprostona/antagonistas & inibidores , Feminino , Meia-Vida , Masculino , Meloxicam , Taxa de Depuração Metabólica , Suínos , Tiazinas/farmacologia , Tiazóis/farmacologia , Tromboxano A2/biossínteseRESUMO
OBJECTIVE: To investigate the sedative effects of guaifenesin in pigs by use of electroencephalography. ANIMALS: 10 Norwegian Landrace pigs (5 castrated males and 5 sexually intact females). PROCEDURE: Guaifenesin (150 mg/kg of body weight, IV) was administered during a 5-minute period. Using a 2-channel referential electrode configuration, electroencephalograms were recorded before, during, and after infusion of guaifenesin. Changes in spectral edge frequency 95% (SEF), median frequency (MED), and total power were evaluated. RESULTS: After administration of guaifenesin, SEF decreased significantly, and total power increased significantly; however, MED did not change significantly. Analysis of the data did not reveal differences between pigs on the basis of sex. CONCLUSIONS AND CLINICAL RELEVANCE: We concluded that guaifenesin synchronized the patterns of electroencephalograms. This is a strong indication that the drug has a sedative effect in pigs.
Assuntos
Eletroencefalografia/veterinária , Guaifenesina/farmacologia , Animais , Eletroencefalografia/efeitos dos fármacos , Feminino , Guaifenesina/administração & dosagem , Infusões Intravenosas , Masculino , Orquiectomia , Valores de Referência , Suínos , Fatores de TempoRESUMO
Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2 µg/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15 ng/mL, with a range from <0.02 ng/mL (below the lower limit of quantification) to 0.25 ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60 µg/kg/min, corresponding to plasma lignocaine concentrations >600 ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20 µg/kg/min lignocaine. Lignocaine at 40 µg/kg/min and dexmedetomidine at 4 µg/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation.
Assuntos
Analgésicos/farmacologia , Dexmedetomidina/farmacologia , Cavalos/metabolismo , Hipnóticos e Sedativos/farmacologia , Lidocaína/farmacologia , Reflexo/efeitos dos fármacos , Analgésicos/sangue , Animais , Cromatografia Líquida/veterinária , Estudos Cross-Over , Dexmedetomidina/sangue , Relação Dose-Resposta a Droga , Estimulação Elétrica , Hipnóticos e Sedativos/sangue , Infusões Intravenosas/veterinária , Lidocaína/sangue , Masculino , Espectrometria de Massas/veterinária , Distribuição AleatóriaRESUMO
In this prospective two-phase experimental trial, 10 pigs were anaesthetized twice with isoflurane only. In the first phase, the individual minimum alveolar concentration (MAC) was determined and in the second phase the effects on withdrawal reflexes of increasing end-tidal isoflurane concentrations (from 1.6% to 2.8%) were assessed. Single, 10 and 60 repeated electrical stimulations were used to evoke withdrawal reflexes which were recorded and quantified by electromyography. Recruitment curves for reflex amplitude for increasing stimulation intensities and isoflurane concentrations were constructed. Isoflurane MAC was 1.9 ± 0.3%. Reflexes evoked by repeated stimulation were suppressed at isoflurane concentrations significantly higher than those which suppressed complex movements during MAC determination (P=0.014 and P=0.006 for 10 and 60 repeated stimuli respectively). Isoflurane up to 2.8% was still not able to abolish reflex activity evoked by repeated stimulations in all pigs. Single stimulation reflexes were suppressed at significantly lower concentrations than repeated stimulation reflexes (P=0.008 and P=0.004 for 10 and 60 repeated stimuli, respectively). Reflex amplitude was significantly correlated with isoflurane concentration (P<0.001, r=-0.85) independent of the individual MAC. The findings indicate that the level at which isoflurane suppresses withdrawal reflexes is dependent on the stimulation paradigm (single vs. repeated electrical stimulation), and there is limited value in expressing reflex withdrawal suppression in terms of MAC as purposeful and reflex movements are independently affected by isoflurane in individual animals.