Hypoadrenocorticism in a kindred of Pomeranian dogs

Three adult Pomeranian dogs, full siblings from 2 litters, were diagnosed with primary hypoadrenocorticism following onset of hypoadrenal crisis. Review of the family history revealed the dogs’ maternal grandmother also had hypoadrenocorticism. All 4 dogs were pedigree-certified by the American Kennel Club. An inherited basis for hypoadrenocorticism is proposed in these Pomeranian dogs.     

Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine,medetomidine, and dexmedetomidine in the horse: a population analysis

The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α₂‐adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half‐maximal effect (IC₅₀) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and mPBPK/PD models for the analysis of clinically obtainable in vivo data.     

Toxicokinetics and absolute oral bioavailability of melamine in broiler chickens

The objective of this study was to investigate the toxicokinetic characteristics of melamine in broilers due to the limited information available for livestock. Melamine was then administered to broiler chickens at an intravenous (i.v.) or oral (p.o.) dosage of 5.5 mg/kg of body weight, and plasma samples were collected up to 48 h. The concentration of melamine in each plasma sample was analyzed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Melamine was measurable up to 24 h after i.v. and p.o. administration. A one‐compartment model was developed to describe the toxicokinetics of melamine in broilers. Following i.v. administration, the values for the elimination half‐life (t_1/2β), the volume of distribution (V_d), and the clearance (CL) were 4.42 ± 1.02 h, 00.52 ± 0.18 L/kg, and 0.08 ± 0.01 L/h/kg, respectively. The absolute oral bioavailability (F) was 95.63 ± 3.54%. The results suggest that most of the administered melamine is favorably absorbed from the alimentary tract and rapidly cleared by the kidneys in broiler chickens.     

Comparative pharmacokinetics and tissue distribution of quinocetone in crucian carp (Carassius auratus), common carp (Cyprinus carpio L.), and grass carp (Ctenopharyngodon idella) following the same experimental conditions

The pharmacokinetics and tissue distribution of quinocetone (QCT) in crucian carp (Carassius auratus), common carp (Cyprinus carpio L.), and grass carp (Ctenopharyngodon idella) were compared after oral administration of QCT (50 mg/kg body weight) at water temperature of 24 ± 1 °C. Similar QCT plasma concentration–time profiles were found in the three species of cyprinid fish at the same dosage regimen and water temperature, which were all fitted two‐compartment open pharmacokinetic model. However, different pharmacokinetic parameters were observed in crucian carp, common carp, and grass carp. The absorption rate constants (K_a) of QCT were 1.65, 1.40 and 1.74/h, respectively and absorption half‐lives (t_1/2kα) were 0.42, 0.49, and 0.40/h, respectively. The distribution half‐life (t_1/2α) was 2.83, 0.67, and 0.88 h, respectively, and elimination half‐lives (t_1/2β) of QCT were 133.97, 63.55, and 40.76 h, respectively. The maximum concentrations (C_max) of QCT in plasma were 0.315, 0.182, and 0.139 μg/mL and the time to peak concentrations (T_p) were 1.45, 0.96, and 1.08 h, respectively. The area under the plasma concentration‐time curves (AUC) were 12.35, 5.99, and 4.52 μg·h/mL, respectively. The distribution volumes (V_d/F) of QCT were calculated as 117.81, 128.71, and 220.10 L/kg, respectively. The tissue analysis showed that a similar regularity was obtained in the three species of cyprinids with a single dose of 50 mg/kg body weight after oral administration at the same water temperature. The tissue concentration of QCT in each fish was in order of liver>kidney>muscle, while the residues of QCT in the three species of cyprinid fish were in order of crucian carp>common carp>grass carp.     

Impact of an experimental PRRSV and Streptococcus suis coinfection on the pharmacokinetics of ceftiofur hydrochloride after intramuscular injection in pigs

This study determined the impact of porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis coinfection on the pharmacokinetic (PK) profile of ceftiofur hydrochloride in pigs after intramuscular (i.m.) injection. Eighteen clinically normal crossbred gilts were assigned by weight into a challenge group (10 pigs) and control group (eight pigs). Pigs in both groups received a single i.m. injection of ceftiofur hydrochloride (Excenel RTU Sterile Suspension; Zoetis) at a 5 mg/kg BW dose. Serial blood samples were collected to characterize the plasma concentration curve. After a 10 days drug washout period, the challenge group was inoculated with 2 mL of PRRSV isolate VR‐2385 (10^5.75 50% tissue culture infective doses per mL) intranasally and 8 days later inoculated S. suis. When clinical disease was evident, the second PK assessment began in both challenge and control groups. Coinfected pigs demonstrated lower values of AUC and C_MAX, but higher values of Cl/F and Vz/F indicating drug kinetics were altered by infection. The data from this study have implications on ceftiofur treatment regimens in diseased pigs.     

Effects of Several Procedures of Ovarian Stimulation on Reproductive Efficiency in Artificially Inseminated Does

Veterinary Research Communications -