Population Pharmacokinetics of Danofloxacin After Single Intramuscular Dose Administration in California Brown Pelicans (Pelecanus occidentalis californicus).

The pharmacokinetics of danofloxacin was investigated in rehabilitated California brown pelicans (Pelecanus occidentalis californicus) after a single intramuscular injection at a dose of 15 mg/kg body weight. The concentration of the drug in plasma was assayed by high-pressure liquid chromatography. A sparse-sampling design was used to reduce the number of samples (1-4 venipunctures) obtained from 24 brown pelicans. A population pharmacokinetic analysis with nonlinear mixed-effects modeling was used to accommodate the sparse-sampling strategy. The nonlinear mixed-effects modeling approach measured both fixed effects (typical values for the population) and random effects (between-subject variability) for this population. A 1-compartment model best represented the concentration-versus-time data after injection. After injection, the elimination half-life, peak concentration, area under the curve, and volume of distribution were 2.76 hours, 2.5 µg/mL, 13.75 µg/h/mL, and 4.35 L/kg, respectively. Rate of absorption was highly variable among the birds. The intramuscular injection of danofloxacin in pelicans at this dose produced plasma concentrations that meet therapeutic targets for bacteria with a minimum inhibitory concentration of ≤0.25 µg/mL. This dose can be used for future studies to evaluate the efficacy of danofloxacin for treating susceptible bacteria.

Gene Transfer of ZMapp Antibodies Mediated by Recombinant Adeno-Associated Virus Protects Against Ebola Infections.

Vectored delivery of the ZMapp antibody cocktail (c2G4, c4G7, and c13C6) by using recombinant adeno-associated viruses (rAAVs) could be useful for preventive immunization against Ebola virus infections because rAAVs can generate long-term antibody expression. Three rAAVs (serotype 9) encoding chimeric ZMapp antibodies were produced by triple-plasmid transfection up to 10 L-scale in WAVE bioreactors using HEK293 cells grown in suspension/serum-free conditions. Efficacy of AAV-c2G4 via intravenous (i.v.), intramuscular (i.m.), and intranasal (i.n.) routes of administration was evaluated in mice with two different doses of 2.7 × 1010 and 13.0 × 1010 vector genomes (vg). The best protective efficacies after Ebola challenge were obtained with the i.v. and i.m. routes. Serum concentrations of ZMapp antibodies positively correlated with survivability. Efficacy of the rAAV-ZMapp cocktail was then evaluated at a higher dose of 30.0 × 1010 vg. It conferred a more robust protection (90% i.v. and 60% i.m.) than rAAV-c4G7 (30%) and rAAV-c13C6 (70%), both administered separately at the same dose. Delivery of rAAV-c2G4 alone achieved up to 100% protection (100% i.v. and 90% i.m.) at the same dose. In conclusion, the preventive treatment was effective in mice. However, no advantage was observed for using the rAAV-ZMapp cocktail in comparison to the utilization of the single rAAV-c2G4.

The contribution of the in-vivo fate of an oil depot to drug absorption.

Sustained release of lipophilic compounds can be achieved with oil depots. These parenteral formulations are generally injected in the vastus lateralis and deltoid muscle. It is known that the absorption rate differs between these two muscles. The reason for this is not fully understood. The aim of the current study was to investigate the fate of an oil depot in different tissues to elucidate whether the disappearance rate of oil is the cause of observed differences in absorption rate. A study with healthy volunteers was conducted to determine 1.0mL oil depots in the vastus lateralis and deltoid muscle for two weeks. The spatial distribution of the oil depots was determined using MRI. Additionally, a study in rats was conducted to microscopically examine the oil immediately and after 31days of injection. All rats were injected with a 0.1mL oil depot with and without benzyl alcohol (BOH), a commonly used excipient in oil depots. In humans, it was shown that all oil depots were equal in volume and surface area directly after injection. Moreover, the disappearance rate for all oil depots was similar; within one week there was no depot visible anymore by MRI. This in contrast to the depots in rats, which were still microscopically visible after 31days. It is concluded from these observations that the oil is dispersed to small droplets in the course of time. The resulting increase in surface area does not lead to an increase in absorption rate however. The results of this paper show that the variation in drug absorption as found for the two muscles is not caused by a distinction in surface areas or disappearance rates of the oil depots. Therefore, it is argued that the local tissue drainage (e.g. lymph flow) plays a considerable role in drug absorption from oil depots, whereby the lymph flow differs between the muscles.

Efeitos sedativos da administração intranasal ou intramuscular de midazolam associado ou não ao butorfanol em periquito autraliano (Melopsitacus undulatus) / Sedative effects of intranasal or intramuscular administration of midazolam with or without butorphanol in budgerigards (Melopsitacus undulatus)

Frequentemente o médico-veterinário é requisitado para realização de diversos procedimentos em aves, os quais geralmente necessitam de sedação ou anestesia geral. Este trabalho teve como objetivo comparar os efeitos sedativos do midazolam (5 mg.kg-1) associado ou não ao butorfanol (1 mg.kg-1) pelas vias de administração intranasal ou intramuscular. Sete periquitos australianos foram submetidos a quatro tratamentos em delineamento do tipo crossover com 15 dias de intervalo. Foram avaliados os períodos de latência, tempos de decúbito dorsal, tempos de sedação, tempos de recuperação, grau de sedação e qualidade de recuperação. Os resultados paramétricos foram avaliados por análise de variância de uma via seguida por teste de Student- Newman-Keuls e os dados não paramétricos foram submetidos ao teste Kruskal-Wallis ambos com 5% de significância. A técnica intranasal demonstrou melhores graus de sedação; no entanto, concluiu-se que ambos os protocolos e as vias de administração avaliados são seguras e viáveis para sedação em periquito australiano.

Often veterinarians have attended various species of birds to perform clinical procedures, which require sedation or general anesthesia. The aim of this study was compare the intranasal or intramuscular sedative effects of midazolam (5 mg.kg-1) with or without butorphanol (1 mg.kg-1). Seven budgerigards (Melopsitacus undulates) were submitted in a crossover design to four treatments. The procedures were performed with 15 days washout. Were evaluated the on set time, dorsal recumbency time duration, total sedation period, total recovery time, sedation degree and recovery quality. The parametric results were analised by one way ANOVA following Student-Newman-Keuls test and non-parametric datas were submitted to Kruskal-Wallis test, both with 5% significance. The intranasal technical demonstrates best degrees of sedation, however, this study concluded that both protocols and the administration routes are safe and viable for sedation in budgerigards