E. Picco

Chronopharmacokinetic Study of Gentamicin in Dogs

The purpose of this experiment was to determine whether the time of day of single intravenous doses of gentamicin affects the drugs pharmacokinetics in dogs maintained under a 12 h light (08:00 to 20:00 h), 12 h dark (20:00 to 08:00 h) cycle. Using a crossover design, 6 mixed‐breed male dogs received a single dose of 2 mg/kg of gentamicin at 8:00 or 20:00 h. Serial blood samples were collected and pharmacokinetic parameters were calculated following each timed dose. The concentration of the antibiotic was lower following the 08:00 h compared to the 20:00 h administration. When gentamicin was administered at 20:00 h, the initial concentration, mean residence time, and area under the disposition curve were significantly higher (p<0.05) and the apparent volume of distribution of the central compartment, apparent volume of distribution, apparent volume of distribution at steady‐state, and total body clearance (1.73±0.55 at 20:00 h versus 3.31±0.67 L/min/kg at 08:00 h) were significantly lower than for the 08:00 h administration (p<0.05). Our results show that the pharmacokinetics of gentamicin exhibits significant temporal variation when administered to dogs at different times of day.

CHRONOTOXICOLOGY OF FLORFENICOL

Sixty 3-month-old homozygote male mice were studied for circadian rhythmicity in the toxicity of florfenicol overdose. Animals were kept under a regimen of 12h light, 12h darkness (12:12 LD) with food and water available ad libitum. The LD50 (median lethal) dose was determined in a preliminary experiment and was administered to groups of 10 mice at six different clock times (hours) after light onset (HALO): 0, 4, 8, 12, 16, and 20 HALO. Cosinor analysis verified a statistically significant (P <. 04) circadian rhythm in the toxic effect (mortality) of florfenicol. Mortality was greatest when the drug was injected 4h after the commencement of the activity span (16 HALO) and least when injected 4h after the start of the diurnal rest span (4 HALO). Mortality was 2.5 times greater when drug injection was given at 16 HALO than at 4 HALO. (Chronobiology International, 18(3), 567–572, 2001)

Use of cholinesterase activity in monitoring chlorpyrifos exposure of steer cattle after topical administration

The aim of this work was to study the pharmacokinetic behavior and the inhibitory effect of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities of chlorpyrifos (CPF) in steer cattle after pour-on administration. Determination of cholinesterase activity in plasma and erythrocyte was carried out according to Ellman kinetic method. CPF was analyzed by gas chromatography. AChE was the predominant form of cholinesterase analyzed, with low levels of BChE in plasma. Following the treatment with CPF, the maximum inhibitory effect on AChE or BChE were 50.88 ± 11.57 and 42.66 ± 12.01%, respectively. The chlorpyrifos plasma concentrations observed were low and they presented a high variability. Chlorpyrifos peak plasma concentration (10.42 ± 4.76 μ g/L) was reached at 8.42 ± 13.97 h. The pesticide was not detected in plasma after 48 h post treatment. The values of area under the curve (AUC) were 118.48 ± 87.46 μ g· h/L and mean resistance time (MRT) were 13.38 ± 10.41 h. The pour-on exposure to the organophosphate chlorpyrifos significantly reduced AChE and BChE activity in steer cattle and the recovery was not reached on 50 days post-treatment.

Pharmacokinetic/Pharmacodinamics Integration of Sulfametazine in buffalo and cattle

Abstract Sulfamethazine is a sulfonamide that presents a broad spectrum of activity, including Gram-positive and Gram-negative bacteria, Chlamydia spp. and some protozoa and it commonly used in ruminants. The aim of our work was to study the possible inter-species differences in the pharmacokinetic behavior and pharmacokinetic/ pharmacodynamic(PK/PD) integration of sulfamethazine after intravenous administration in buffalo and bovine. A single intravenous dose of 60 mg/kg was administered to six bovine and five buffalo (3-4 month old and weighting 120±15kg). Plasma concentrations of sulfamethazine were determined by high performance liquid chromatography. Differences between bovine and buffalo calves were found in t½λ (buffaloes: t1/2λ =6.17±0.58h; bovine t1/2λ=7.46±1.05h), Cl (buffaloes: 45.31ml/h·kg; bovines 30.34ml/h·kg). As a consequence of the lower clearance in bovines, the AUC and t½λ values were higher in this species. Important differences between bovine and buffalo exist for microorganisms that have a MIC value<32µg/ml related to time over minimum inhibitory concentration and weighted AUC.

Pharmacokinetics of sodium meclofenamate in pre-ruminant cattle

The pharmacokinetic profile of sodium meclofenamate, a non-steroidal antiinflammatory drug, was determined in six pre-ruminant calves after intravenous and intramuscular administration at a dose of 2.2mg/kg of body weight. Meclofenamate concentrations were measured using a high performance liquid chromatography assay. The pharmacokinetics of sodium meclofenamate after intravenous and intramuscular administration to calves were characterised by a rapid distribution phase (t½α), 15.45±4.85min and 23.14±7.24min for the intravenous and intramuscular administration, respectively, followed by a longer elimination phase (t½β) after intramuscular treatment (17.55±6.52h.). The apparent volume of distribution (Vd) of the drug after intravenous administration was moderate (0.72±0.12l/kg), and high (3.51±1.05l/kg) after intramuscular administration. This can be explained by the flip-flop effect or by enterohepatic shunting. The bioavailability achieved after intramuscular administration was 61%.