RESUMEN
Since vaccination may not prevent disease, antiherpetic drugs have been investigated for the therapy of several equine herpesviruses. Drug efficacy has been assessed in horses with disease, but most evidence is in vitro, in other species, or empirical. Oral valacyclovir is most often administered in the therapy of equine herpesvirus type-1 (EHV-1) to protect adult horses from equine herpesvirus myeloencephalopathy, while oral acyclovir is frequently administered for EHV-5 infection in the therapy of equine multinodular pulmonary fibrosis. Other antiherpetic drugs are promising but require further investigation. Several topical drugs are also empirically used in the therapy of equine viral keratitis.
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Antivirales/uso terapéutico , Infecciones por Herpesviridae/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/virología , Animales , Encefalomielitis/tratamiento farmacológico , Encefalomielitis/veterinaria , Encefalomielitis/virología , Infecciones por Herpesviridae/tratamiento farmacológico , Herpesvirus Équido 1/aislamiento & purificación , Caballos , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/veterinaria , Fibrosis Pulmonar/virologíaRESUMEN
OBJECTIVE: To determine (1) the dose of liposomal bupivacaine (LB) to eliminate grade 2 of 5 lameness, the (2) duration of analgesia of LB versus bupivacaine hydrochloride (BH), and (3) LB pharmacokinetics versus BH. METHODS: A reversible lameness model was validated in conditioned Thoroughbred horses (n = 12), aged 3 to 10 years. A dose-response trial compared subjective and objective lameness following abaxial sesamoid block with 25 mg BH/nerve or 30, 60, or 133 mg LB/nerve (n = 3/group). The LB dose that eliminated lameness and reduced lameness for the longest was used for blinded, randomized, crossover pharmacokinetic/pharmacodynamic trials (n = 12/group). Data were analyzed using a paired t test or Wilcoxon signed-rank test, P < .05. RESULTS: The 133-mg/nerve dose of LB eliminated lameness in 3 of 3 horses in the dose-response trial, and lameness returned at 6, 36, and 72 hours. In the pharmacokinetic/pharmacodynamic trials, time to return of lameness greater than or equal to starting lameness was longer for LB compared to BH on subjective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 4 to 12 hours) and objective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 2 to 6 hours) evaluations. The terminal half-life was not different between formulations (LB, 17.8 hours ± 10.1; BH, 12.4 hours ± 6.3); however, LB had increased area under the concentration-versus-time curve from time 0 to infinity (LB, 388 ng·h/mL ± 117; BH, 63 ng·h/mL ± 18) and mean residence time (LB, 17.6 hours ± 2.4; BH, 3.9 hours ± 1.6). CONCLUSIONS: Liposomal bupivacaine analgesia duration was greater than BH, but the median time until lameness returned was only 12 hours. Bupivacaine is quantifiable in serum and urine beyond loss of clinical effect. CLINICAL RELEVANCE: A single, high-dose injection of LB is not effective for providing perineural analgesia over several days. Bupivacaine is detectable after the effect of the drug has worn off.
RESUMEN
BACKGROUND: Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra-articular (IA) administration. HYPOTHESIS/OBJECTIVES: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens. ANIMALS: Eight healthy neonatal foals. METHODS: Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 µg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility. RESULTS: Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean µg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.
Asunto(s)
Amicacina , Animales Recién Nacidos , Antibacterianos , Animales , Amicacina/farmacocinética , Amicacina/administración & dosificación , Amicacina/sangre , Caballos/sangre , Inyecciones Intraarticulares/veterinaria , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Masculino , Femenino , Inyecciones Intravenosas/veterinariaRESUMEN
ostmortem redistribution (PMR), a well-known phenomenon in forensic toxicology, can result in substantial changes in drug concentrations after death, depending on the chemical characteristics of the drug, blood collection site, storage conditions of the body and postmortem interval (PMI). Limited PMR data are available for ∆9-tetrahydrocannabinol (THC), the primary psychoactive component in Cannabis sativa. PMR was evaluated after controlled cannabis inhalation via a smoking machine and exposure chamber in New Zealand white rabbits. Necropsies were performed on five control rabbits immediately after euthanasia, whereas 27 others were stored at room temperature (21°C) or refrigerated conditions (4°C) until necropsy at 2, 6, 16, 24 or 36 h after death. THC and its Phase I and glucuronidated Phase II metabolites were quantified in blood, vitreous humor, urine, bile and tissues by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Under refrigerated temperature, heart blood THC concentrations significantly increased at PMI 2 h in rabbits, whereas peripheral blood THC concentrations showed a significant increase at PMI 16 h. Central:peripheral blood and liver:peripheral blood ratios for THC ranged from 0.13 to 4.1 and 0.28 to 8.9, respectively. Lung revealed the highest THC concentrations, while brain and liver exhibited the most stable THC concentrations over time. This report contributes much needed data to our understanding of postmortem THC behavior and can aid toxicologists in the interpretation of THC concentrations in medicolegal death investigations.
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Cannabis , Alucinógenos , Conejos , Animales , Cannabis/toxicidad , Dronabinol/análisis , Temperatura , Autopsia , Cambios Post MortemRESUMEN
The major objective of the study was to assess the pharmacokinetics of tetracycline administered orally to fasted and nonfasted American alligators (Alligator mississippiensis) at 50 mg/kg. Plasma levels of tetracycline were determined using high-performance liquid chromatography with ultraviolet detection. The concentration versus time curve was analyzed using a compartmental modeling technique. A one-compartment model with first-order absorption and elimination, as well as a lag time to absorption, best described the data. The area under the curve and mean residence time values differed significantly between the fasted and nonfasted groups. Based on the results of this study, tetracycline suspension administered once orally at 50 mg/kg to American alligators is not expected to reach plasma concentrations above the breakpoint minimum inhibitory concentration of 4 microg/ml for susceptible organisms.
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Caimanes y Cocodrilos/sangre , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Tetraciclina/administración & dosificación , Tetraciclina/farmacocinética , Administración Oral , Animales , Antibacterianos/sangre , Área Bajo la Curva , Esquema de Medicación , Semivida , Tetraciclina/sangreRESUMEN
The coccidian protozoan, Caryospora cheloniae, has been associated with severe enteritis and encephalitis in immature farm-raised green turtles (Chelonia mydas) in the Cayman Islands, immature green turtles off the coast of Florida, and immature stranded sea turtles in Australia. An effective anti-coccidial drug that is both orally absorbed and well-distributed throughout the body is needed for treatment of turtles diagnosed with coccidiosis in rehabilitation facilities. Ponazuril is a triazine antiprotozoal drug that is approved in the USA for the treatment of another Apicomplexan, Sarcocystis neurona, and has also been successfully used in the therapy of other coccidian parasites. The objective of this study was to perform an oral dose-ranging pilot study (10-100 mg/kg of body weight ponazuril) in green turtles (N = 9), followed by oral administration of ponazuril at 100 mg/kg body weight (N = 8) to assess its disposition. Another goal of this study was to optimize the method of oral drug administration to green turtles. Plasma ponazuril concentrations were quantified using high performance liquid chromatography (HPLC). Standard compartmental models were fit to the data. Ponazuril was absorbed after oral administration at 100 mg/kg BW, with a maximum plasma concentration of 3.3 µg/ml. Dose-dependent pharmacokinetic parameters only weakly correlated with the dose rate, apparently due to considerable pharmacokinetic variability observed between turtles. Administration of ponazuril in gelatin capsules using a balling gun was deemed the least variable and most successful method of drug administration. Further studies are needed to evaluate the safety and efficacy of ponazuril in sea turtles with coccidiosis.
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Tortugas , Animales , Modelos Epidemiológicos , Proyectos Piloto , TriazinasRESUMEN
OBJECTIVE: To determine effects of pituitary pars intermedia dysfunction (Cushing's disease) and age on fecal egg count and time to egg reappearance after anthelmintic treatment in horses residing in similar environments. DESIGN: Cross-sectional study. ANIMALS: 29 healthy horses (4 to 35 years old) and 13 horses with PPID (13 to 33 years old). PROCEDURES: Fecal egg counts were performed by use of a modified Wisconsin flotation method at 2-week intervals before and after ivermectin treatment. RESULTS: Horses with PPID had higher fecal egg counts before and 8, 10, and 12 weeks after ivermectin treatment, compared with counts for site-matched healthy horses. There was no difference in the period for < 90% reduction in fecal egg counts between the 2 groups. Age did not affect fecal egg counts at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: For similar environmental conditions, horses with PPID were more likely to have higher fecal egg counts than were healthy horses. Therefore, horses with PPID may need to have a more aggressive parasite prevention program than do healthy horses. Age did not affect fecal egg counts or time to egg reappearance after anthelmintic treatment, which suggested age alone does not likely require special consideration when designing a parasite control program for adult horses.
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Envejecimiento , Antihelmínticos/uso terapéutico , Helmintiasis Animal/tratamiento farmacológico , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de la Hipófisis/veterinaria , Adenohipófisis Porción Intermedia , Animales , Heces/parasitología , Femenino , Helmintiasis Animal/parasitología , Enfermedades de los Caballos/parasitología , Caballos , Masculino , Recuento de Huevos de Parásitos/veterinaria , Enfermedades de la Hipófisis/complicaciones , Factores de TiempoRESUMEN
Zoonotic monkey B virus (Macacine alphaherpesvirus 1; BV) infections are extremely serious and usually fatal. Drugs currently used for treatment were developed for the treatment of herpes simplex virus but are less effective against BV. Effective suppression of viral replication in the skin could prevent the virus from invading the nervous system. To test this hypothesis, the efficacy of topical administration of several drugs against lethal BV infection was evaluated in female BALB/c mice that were infected by scarification. Drugs were then applied to the site of inoculation. As 3% preparations, most drugs were only minimally effective or ineffective. In contrast, ganciclovir and cidofovir were very effective. The ED50 for cidofovir was 0.007%, compared with 1.1% for ganciclovir. At 0.5%, cidofovir protected against both death and neurologic signs, whereas 5% ganciclovir only protected against death but not neurologic involvement. All genotypes of BV were equally susceptible to cidofovir and ganciclovir. For maximal effectiveness, treatment with both cidofovir and ganciclovir had to be initiated within 8 h of infection. Cidofovir was completely protective when administered only on the day of infection, whereas a minimum of 5 d of treatment was required for maximal ganciclovir efficacy. These studies showed that topical cidofovir treatment started soon after BV exposure was very effective in preventing BV from invading the nervous system, whereas ganciclovir treatment was only partially effective. In addition, cidofovir was protective against a ganciclovir-resistant BV mutant, whereas ganciclovir was not. These studies showed that topical cidofovir treatment started soon after BV exposure is more effective than ganciclovir in preventing BV from invading the CNS.
Asunto(s)
Antivirales/farmacología , Cidofovir/farmacología , Ganciclovir/farmacología , Infecciones por Herpesviridae/prevención & control , Herpesvirus Cercopitecino 1/efectos de los fármacos , Ratones , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones Endogámicos BALB C , Profilaxis Pre-Exposición , Enfermedades Cutáneas Virales/patología , Enfermedades Cutáneas Virales/prevención & controlRESUMEN
Monkey B virus (Macacine herpesvirus 1; BV) is an alpha-herpesvirus of macaques that causes serious infections in humans. A spontaneous mutant resistant to penciclovir (PCV) was isolated. Several genes were sequenced to identify mutations potentially responsible for PCV resistance. A single nucleotide deletion in the thymidine kinase (TK) gene was identified. To confirm its role in PCV resistance, several TK recombinants were constructed. A TK-deletion virus and a recombinant carrying the mutation were both resistant to PCV, while a revertant was PCV-sensitive. These results demonstrate that spontaneous drug-resistant mutants of BV do occur and that the BV TK is responsible for sensitivity to PCV.
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Aciclovir/análogos & derivados , Farmacorresistencia Viral/genética , Herpesvirus Cercopitecino 1/genética , Inhibidores de la Transcriptasa Inversa/farmacología , Timidina Quinasa/genética , Aciclovir/farmacología , Animales , Guanina , Herpesvirus Cercopitecino 1/efectos de los fármacos , Humanos , Mutación , Proteínas Virales/genéticaRESUMEN
OBJECTIVE: To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg). PROCEDURES: Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration. RESULTS: Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.
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Agonistas alfa-Adrenérgicos/farmacología , Periodo de Recuperación de la Anestesia , Anestésicos Intravenosos/farmacología , Caballos/fisiología , Isoflurano/análogos & derivados , Propofol/farmacología , Xilazina/farmacología , Agonistas alfa-Adrenérgicos/administración & dosificación , Anestésicos por Inhalación/administración & dosificación , Anestésicos Intravenosos/administración & dosificación , Animales , Dióxido de Carbono/metabolismo , Estudios Cruzados , Desflurano , Inyecciones Intravenosas/veterinaria , Isoflurano/administración & dosificación , Propofol/administración & dosificación , Propofol/sangre , Factores de Tiempo , Xilazina/administración & dosificaciónRESUMEN
OBJECTIVE: To characterize the behavior of horses recovering in the Anderson Sling Suspension System after 4 hours of desflurane anesthesia and postdesflurane intravenous (IV) administration of propofol and xylazine. STUDY DESIGN: Experimental study. ANIMALS: Healthy horses (n=6), mean+/-SEM age 12.3+/-1.8 years; mean weight 556+/-27 kg. METHODS: Each horse was anesthetized with xylazine, diazepam, and ketamine IV and anesthesia was maintained with desflurane in O(2). At the end of 4 hours of desflurane, each horse was positioned in the sling suspension system and administered propofol-xylazine IV. Recovery events were quantitatively and qualitatively assessed. Venous blood was obtained before and after anesthesia for biochemical and propofol analyses. RESULTS: Anesthetic induction and maintenance were without incident. Apnea commonly accompanied propofol administration. All horses had consistent recovery behavior characterized by a smooth, careful, atraumatic return to a standing posture. CONCLUSIONS: Results of this study support careful, selective clinical use of desflurane, propofol-xylazine, and the Anderson Sling Suspension System to atraumatically transition horses with high anesthetic recovery risk to a wakeful standing posture. CLINICAL RELEVANCE: Technique choices to facilitate individualized, atraumatic recovery of horses from general anesthesia are desirable. Use of IV propofol and xylazine to transition horses from desflurane anesthesia during sling recovery to standing posture may facilitate improved recovery management of high-injury risk equine patients requiring general anesthesia.
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Anestesia por Inhalación/veterinaria , Anestésicos por Inhalación , Anestésicos Intravenosos , Caballos , Inmovilización/veterinaria , Isoflurano/análogos & derivados , Propofol , Xilazina , Periodo de Recuperación de la Anestesia , Animales , Desflurano , Femenino , Caballos/cirugía , Masculino , Monitoreo Fisiológico/veterinaria , Propofol/sangreRESUMEN
Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.
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Analgésicos Opioides/farmacocinética , Buprenorfina/farmacocinética , Enfermedades de los Perros/tratamiento farmacológico , Perros/metabolismo , Dolor/veterinaria , Administración Oral , Analgésicos Opioides/sangre , Animales , Área Bajo la Curva , Disponibilidad Biológica , Buprenorfina/sangre , Cromatografía de Gases , Cromatografía Líquida de Alta Presión/veterinaria , Estudios Cruzados , Enfermedades de los Perros/sangre , Perros/sangre , Relación Dosis-Respuesta a Droga , Inyecciones Intravenosas/veterinaria , Absorción Intestinal/efectos de los fármacos , Espectrometría de Masas , Dolor/sangre , Dolor/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Equine herpesvirus-5 is commonly isolated from the lungs of horses with EMPF, suggesting an etiological link. Valacyclovir is used empirically to treat EMPF; however, no data is available concerning its impact on EHV-5 viral kinetics. OBJECTIVES: To determine the effect of oral administration of valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS) and BALF in horses with EMPF. ANIMALS: Six horses diagnosed with EMPF. METHODS: A prospective clinical trial was performed. Horses received 10 days of PO administered valacyclovir (loading dose 30 mg/kg, maintenance dose 20 mg/kg). Blood, NS, and BALF were collected for EHV-5 viral kinetics analyses during treatment. Blood and NS were collected every other day. BALF was collected on day 0 and day 10. RESULTS: There was no statistical difference in median EHV-5 viral load between day 0 and day 10 for all samples tested. In blood median EHV-5 viral load was 7676 (range 575-39 781) on day 0 and 6822 (range 1136-18 635) glycoprotein B (gB) gene copies per million cells on day 10. For NS median EHV-5 viral load was 2.944 × 106 (range 184 691-3.394 × 109 ) on day 0 and 8.803 × 106 (range 251 186-9.868 × 108 ) gB gene copies per million cells on day 10. For BALF median EHV-5 viral load was 59,842 (range 61-315 655) on day 0 and 185 083 (range 3562-542 417) gB gene copies per million cells on day 10. CONCLUSIONS AND CLINICAL IMPORTANCE: Valacyclovir might not be an effective short-term antiviral treatment but efficacy in treatment of EMPF is unknown.
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Gammaherpesvirinae , Infecciones por Herpesviridae/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Fibrosis Pulmonar/veterinaria , Valaciclovir/uso terapéutico , Animales , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Líquido del Lavado Bronquioalveolar , ADN Viral , Relación Dosis-Respuesta a Droga , Femenino , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/virología , Caballos , Masculino , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/virología , Valaciclovir/administración & dosificación , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND: Transdermal fentanyl is used clinically in horses based on pharmacokinetic data and antinociceptive effects documented in other species. HYPOTHESIS: Fentanyl IV administration increases both visceral and somatic nociceptive threshold in conscious horses. ANIMALS: Six clinically normal horses, each fitted with a permanent gastric cannula. METHODS: Visceral nociception was evaluated with 2 methods of threshold detection--olorectal distention and duodenal distention. Somatic nociception was assessed by measurement of thermal threshold. Fentanyl was administered as an increasing stepwise infusion followed by a continuous-rate infusion for a total of 2 hours. There were 4 doses of fentanyl and 1 dose each of saline and xylazine administered to each horse. Serum fentanyl concentrations were measured and the resulting data were used to determine pharmacokinetic parameters for each horse. All data were analyzed by means of a 3-factor analysis of variance followed by either a simple t test or a Bonferroni t test for multiple comparisons. RESULTS: Fentanyl administration did not result in significant changes in duodenal or colorectal distention threshold. Thermal threshold showed an increased trend at the 15-minute time point for the highest fentanyl group only, with a corresponding mean serum fentanyl concentration of 7.82 +/- 2.10 ng/mL. Two horses in this group became agitated and tachycardic during the first 15 minutes of the infusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Fentanyl did not produce a significant antinociceptive effect at the doses used, 2 of which resulted in serum concentrations above the nociceptive threshold in other species.
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Analgésicos Opioides/farmacología , Fentanilo/farmacología , Caballos/fisiología , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/veterinaria , Analgésicos Opioides/farmacocinética , Análisis de Varianza , Animales , Temperatura Corporal/efectos de los fármacos , Colon/efectos de los fármacos , Femenino , Fentanilo/farmacocinética , Motilidad Gastrointestinal/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Caballos/metabolismo , Inyecciones Intravenosas/veterinaria , Masculino , Distribución Aleatoria , Respiración/efectos de los fármacos , Estómago/efectos de los fármacosRESUMEN
The objective of this study was to determine the serum pharmacokinetics of terbutaline in healthy cows. In the initial experiment, terbutaline was administered once as an intravenous (i.v.) bolus to 6 near-term pregnant beef cows within 24 h after parturition at a low but therapeutically relevant dose, 5 microg/kg. A 2nd experiment was conducted in the same cows with a higher dose, 0.5 mg/kg, but an otherwise similar experimental design. The serum concentration of terbutaline was determined by means of high-performance liquid chromatography with fluorescence detection in both experiments. After i.v. administration of 0.5 mg/kg, the mean peak serum concentration, residence time, and half-life were 708.22 (standard deviation 509.6) ng/mL, 6.75 (3.6) min, and 6.93 (2.4) min, respectively. The results indicate that terbutaline is rapidly eliminated from the bloodstream after i.v. administration in cattle, falling below the assay's limit of detection 30 min after administration.
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Terbutalina/farmacocinética , Tocolíticos/farmacocinética , Animales , Área Bajo la Curva , Bovinos , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida de Alta Presión/veterinaria , Relación Dosis-Respuesta a Droga , Femenino , Fluorescencia , Semivida , Inyecciones Intravenosas/veterinaria , EmbarazoRESUMEN
OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differentially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 µg/mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1-infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.
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Aciclovir/análogos & derivados , Antivirales/uso terapéutico , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1 , Enfermedades de los Caballos/tratamiento farmacológico , Valina/análogos & derivados , Aciclovir/uso terapéutico , Animales , Femenino , Fiebre/tratamiento farmacológico , Fiebre/veterinaria , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/fisiopatología , Enfermedades de los Caballos/fisiopatología , Caballos , Premedicación/veterinaria , Valaciclovir , Valina/uso terapéutico , Viremia/veterinaria , Replicación Viral/efectos de los fármacosRESUMEN
The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.
Asunto(s)
Aciclovir/farmacocinética , Antivirales/farmacocinética , Caballos/metabolismo , Aciclovir/administración & dosificación , Aciclovir/sangre , Administración Oral , Animales , Antivirales/administración & dosificación , Antivirales/sangre , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Femenino , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1 , Enfermedades de los Caballos/tratamiento farmacológico , Inyecciones Intravenosas/veterinaria , MasculinoRESUMEN
OBJECTIVE: To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses. ANIMALS: 8 healthy adult horses. PROCEDURES: A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV administration. For oral administration, blood samples were collected 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, and 12 hours after the first dose and 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 hours after the last dose. RESULTS: Elimination of pentoxifylline was rapid after IV administration. After oral administration, pentoxifylline was rapidly absorbed and variably eliminated. Higher serum concentrations of pentoxifylline and apparent bioavailability were observed after oral administration of the first dose, compared with values after administration of the last dose on day 8 of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, oral administration of 10 mg of pentoxifylline/kg results in serum concentrations equivalent to those observed for therapeutic doses of pentoxifylline in humans. Twice daily administration appears to be appropriate. However, serum concentrations of pentoxifylline appear to decrease with repeated dosing; thus, practitioners may consider increasing the dosage if clinical response diminishes with repeated administration.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Caballos/metabolismo , Pentoxifilina/farmacocinética , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/sangre , Estudios Cruzados , Preparaciones de Acción Retardada/farmacología , Femenino , Caballos/sangre , Inyecciones Intravenosas/veterinaria , Masculino , Pentoxifilina/administración & dosificación , Pentoxifilina/sangre , Distribución AleatoriaRESUMEN
Glucosamine (GS) is commonly administered as a nutritional supplement to support joint function. Although many supplements are available, the effect of formulation on oral absorption in dogs is unknown. The purpose of this study was to determine the relative bioavailability of GS for liquid, chewable, and tablet formulations containing GS sulfate or hydrochloride and chondroitin sulfate. In a randomized cross-over design, supplements were administered daily for 8 days with a 1 wk washout period between treatments. Liquid or Tablet A was administered to four dogs, whereas Liquid or Tablet B was administered to four additional dogs. When nutraceutical exposure was normalized to the administered dose of GS free base, similar relative bioavailabilities were determined for all three formulations. However, the dose-normalized maximum plasma GS concentration was higher for the liquid supplement (5.5 ± 0.5 µg/mL) than for the two tablets (3.1 ± 0.6 and 2.1 ± 0.6 µg/mL, P < 0.001). Similarly, the time at which maximal plasma GS concentrations occurred was shorter for the liquid formulation (0.7 ± 0.5 hr) than for the two tablets (4.2 ± 0.6 and 5.0 ± 0.6 hr, P < 0.001). These data show that the formulation of joint supplements affects the oral absorption of GS in dogs.
Asunto(s)
Perros/metabolismo , Glucosamina/administración & dosificación , Glucosamina/farmacocinética , Administración Oral , Animales , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Suplementos Dietéticos , Perros/sangre , Absorción Intestinal , Masculino , ComprimidosRESUMEN
OBJECTIVE: To determine pharmacokinetics of azathioprine (AZA) and clinical, hematologic, and serologic effects of i.v. and oral administration of AZA in horses. ANIMALS: 6 horses. PROCEDURE: In study phase 1, a single dose of AZA was administered i.v. (1.5 mg/kg) or orally (3.0 mg/kg) to 6 horses, with at least 1 week between treatments. Blood samples were collected for AZA and 6-mercaptopurine (6-MP) analysis 1 hour before and at predetermined time points up to 4 hours after AZA administration. In study phase 2, AZA was administered orally (3 mg/kg) every 24 hours for 30 days and then every 48 hours for 30 days. Throughout study phase 2, blood samples were collected for CBC determination and serum biochemical analysis. RESULTS: Plasma concentrations of AZA and its metabolite, 6-MP decreased rapidly from plasma following i.v. administration of AZA, consistent with the short mean elimination half-life of 1.8 minutes. Oral bioavailability of AZA was low, ranging from 1% to 7%. No horses had abnormalities on CBC determination or serum biochemical analysis, other than 1 horse that was lymphopenic on day 5 and 26 of daily treatment. This horse developed facial alopecia from which 1 colony of a Trichophyton sp was cultured; alopecia resolved within 1 month after the study ended. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, no adverse effects were observed with long-term oral administration of AZA to horses, although 1 horse did have possible evidence of immunosuppression with chronic treatment. Further investigation of the clinical efficacy of AZA in the treatment of autoimmune diseases in horses is warranted.