ABSTRACT
The pharmacokinetics of single-dose administration of orbifloxacin were determined in Japanese quail (Coturnix japonica) at dosages of 5 mg/kg intravenous (i.v. n = 12) and 7.5 mg/kg oral (p.o.; n = 5), 10 mg/kg p.o. (n = 5), 15 mg/kg p.o. (n = 12) and 20 mg/kg p.o. (n = 5) via HPLC. Orbifloxacin minimal inhibitory concentrations (MICs) against 22 microbial isolates from various bird species were performed to calculate pharmacodynamic surrogate markers. The concentration-time data were analyzed using a naïve pooled data (NPD) approach and compartmental and noncompartmental methods. Steady-state volume of distribution (Vd(ss)) and total body clearance (Cl) after i.v. administration were estimated to be 1.27 L/kg and 0.60 L/h·kg, respectively. Following 15 and 20 mg/kg p.o. dose, bioavailability was 102% and 117%, respectively. The harmonic mean of the corresponding terminal half-lives (T(1/2) λ(z) ) across all the dose groups was 1.71 h. The C(max) /MIC(90) and AUC(0∞24) /MIC(90) for the 15 and 20 mg/kg p.o. doses were ≥5.22 and ≥8.98, and ≥25.80 and ≥39.37 h, respectively. The results of this study suggest that 20 mg/kg orbifloxacin p.o. would be a rational daily dose to treat susceptible infections in Japanese quail not intended for food consumption. For more sensitive bacterial organisms, 15 mg/kg p.o. may also be effective.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Ciprofloxacin/analogs & derivatives , Coturnix/metabolism , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Biological Availability , Chromatography, High Pressure Liquid/veterinary , Ciprofloxacin/administration & dosage , Ciprofloxacin/pharmacokinetics , Ciprofloxacin/pharmacology , Cross-Over Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Escherichia coli/drug effects , Female , Injections, Intravenous/veterinary , Male , Microbial Sensitivity Tests/veterinary , Pasteurella/drug effects , Staphylococcus/drug effectsABSTRACT
The enantioselective pharmacokinetics of single dose (2 mg/kg) racemic carprofen (CPF) were evaluated in adult New Zealand white rabbits after intravenous (i.v.) and subcutaneous (s.c.) dose. Six rabbits were utilized in a two-way randomized crossover study and serial blood samples were collected. Plasma CPF concentrations were determined by high-performance liquid chromatography. After i.v. and s.c. racemic CPF administration, plasma concentration-time curves were best described by a two-compartment open model and a one-compartment model, respectively. The S(+) CPF enantiomer predominated in plasma following both routes of administration. Mean observed clearance of R(-)-CPF (82.17 +/- 13.70 mL/h.kg) was more rapid than for S(+)-CPF (27.92 +/- 7.07 mL/h.kg; P < 0.001). T(1/2)lambda z was shorter for R(-)-CPF than S(+)-CPF after both i.v. (1.03 and 2.99 h, respectively) and s.c. (1.94 and 4.14 h, respectively) dosing. Mean AUC(0-->infinity) ratios for R(-):S(+)-CPF were approximately 1:3 for both routes of administration. Mean residence time of R(-)-CPF was shorter than of S(+)-CPF (1.06 +/- 0.29 h, 3.45 +/- 0.50 h; P < 0.001) and R(-)- and S(+)-CPF volumes of distribution at steady state were 85.00 +/- 14.42 and 94.39 +/- 18.66 mL/kg, respectively after i.v. administration. The mean s.c. bioavailability [F (%)] for both R(-)- and S(+)-CPF was high, 94.4 +/- 22.8 and 91.0 +/- 35.7%, respectively.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Carbazoles/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/blood , Area Under Curve , Biological Availability , Carbazoles/administration & dosage , Carbazoles/blood , Female , Half-Life , Injections, Intravenous , Injections, Subcutaneous , Male , Metabolic Clearance Rate , Rabbits , StereoisomerismABSTRACT
Pharmacokinetic studies of antibiotics in South American camelids are uncommon, therefore drugs are often administered to llamas and alpacas based on dosages established in other domestic species. The disposition of ceftiofur sodium was studied in llamas following intramuscular administration and in alpacas following intravenous and intramuscular administration. Eleven adult llamas were given ceftiofur sodium by intramuscular injection. Each animal received either a standard dose of 2.2 mg/kg or an allometrically scaled dose ranging from 2.62 to 2.99 mg/kg in a crossover design. Ten adult alpacas were given ceftiofur sodium by intravenous and intramuscular injections. Each animal received a standard dosage of 1 mg/kg or an allometrically scaled dose ranging from 1.27 to 1.44 mg/kg i.v., and 1.31-1.51 mg/kg i.m. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and 72 h after administration of the ceftiofur. Pharmacokinetic parameters of ceftiofur in llamas and alpacas were similar following i.m. dosing at both dose levels. The only differences noted were in the total AUC between dose levels, but the AUC/dose values were not different. A sequence effect was noted in the alpaca data, which resulted in lower AUCs for the second dose when the i.v. dose was given first, and with higher AUCs for the second dose when the i.m. dose was given first. Overall, ceftiofur pharmacokinetics in llamas and alpacas are similar, and also very similar to reported parameters for sheep and goats.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Camelids, New World/metabolism , Cephalosporins/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Cephalosporins/administration & dosage , Cephalosporins/blood , Cross-Over Studies , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinaryABSTRACT
The gelling polysaccharide produced by a species of Enterobacter (NCIB 11870) contains L-fucose, D-glucose, and D-glucuronic acid in the ratios 1:2:1. Analysis of the methylated and methylated, carboxyl-reduced polysaccharide revealed terminal non-reducing glucose, (1----3)-linked fucose, (1----3,1----4)-linked glucose, and (1----4)-linked glucuronic acid in the ratios 1:1:1.2:0.8. From the results of Smith degradation of the polysaccharide and spectroscopic studies of the acidic tetra- and octa-saccharides produced by bacteriophage-induced enzymic depolymerization of the polysaccharide, the following tetrasaccharide repeating-unit is proposed. (Formula: see text). This repeating-unit is identical to that of the capsular polysaccharide produced by Klebsiella aerogenes serotype K54 except for the absence of O-acetyl groups. The effects of the O-acetyl groups on the secondary structure and rheological properties of these polysaccharides are discussed.
Subject(s)
Enterobacter/immunology , Enterobacteriaceae/immunology , Polysaccharides, Bacterial/isolation & purification , Carbohydrate Conformation , Carbohydrate Sequence , Indicators and Reagents , Klebsiella/immunology , Oligosaccharides/analysis , Species SpecificityABSTRACT
A 7-year-old girl twice developed severe hypernatremia (serum sodium values up to 194 mEq/l) without obvious cause. The ability of her kidneys to conserve water was normal, and increasing her plasma osmolality stimulated an appropriate ADH response. Unable to excrete a water load, her kidneys continued to conserve water even with a serum sodium concentration of 133 mEq/l. She was never thirsty and did not ingest sufficient fluid by choice. Although there was no demonstrable anatomic lesion, we postulate a localized defect of her thirst center. This may have modified release of ADH and resulted in an inability to dilute the urine by interrupting a pathway that could exist from the thirst center to the supraoptic nuclei. A therapeutic regimen based on these studies has prevented further hypernatremia.