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Proceedings of the 21st ipvs congress
Tetracycline administered in water: pharmacokinetics and lessons
for administration of other medications via water
Sharon Mason1 Ronald Baynes1 Glen Almond1 Jim Riviere1 Alan Scheidt2
1. North Carolina State University, Raleigh, NC, USA; 2. Pfi zer Animal Health, Kalamazoo, MI, USA
Table 1: Pharmacokinetic parameters of tetracycline
The use of medications dosed in water is a common occurrence
in swine medicine. However, no published pharmacokinetic (PK)
studies are available on tetracycline dosed in water in swine
or the factors that determine the plasma concentration levels achieved in medicated swine.
Materials and Methods
Study. Twenty-four castrated male swine, 9 weeks of age (early
grower), divided into 4 groups (n=6), were exposed to tetracy-
aCmax, maximum plasma concentration; Css, steady state concentration; Cl, clearance;
cline powder administered exclusively in water at 0, 125, 250
Vd, volume of distribution at steady state, F, bioavailability.
and 500 ppm via a randomized block design (1). Blood samples were collected before and at 4, 8, 12, 24, 32, 48, 56, 72, 80, 96 and 104 h post-exposure. All plasma samples were assayed
using HPLC-UV with a LOD of 0.05 μg/mL within 7 days of collec-
Tetracycline water medication PK parameters were consistent
tion (1). Statistical analysis across groups and covariates using a
with values from the literature. Plasma levels were lower than
one-way ANOVA (SAS 9.1, Cary NC) revealed no bias. All animals
those from observational studies in which animals were fasted.
were healthy and the protocol met IACUC standards at NC State
Low plasma concentrations may be due to low oral bioavailabil-
University College of Veterinary Medicine.
ity and cation chelation of tetracycline by food.
Pharmacokinetic analysis. Non-compartmental analysis was
Body weight, water consumption and water concentrations of
performed on plasma concentrations. Population PK analysis
the medication are the most important covariates for population
using a one-compartmental model was performed in Phoe-
PK analysis. Temperature was important in the initial study; how-
nix WinNonMix NLME 1.0 (Pharsight, Mountain View, CA). The
ever, ambient temperatures were not recorded for validation
developed model was improved and validated by two additional
data. Temperatures appear important when large fl uctuations
data sets from Dorr et al (2). Potential covariates considered
are present, because this changes the baseline water consump-
were body weight, ambient temperature, water consumption,
water concentration of tetracycline and health status of the animal.
Population analysis on other medications is necessary for further validation of the above factors and to elucidate other potential
covariates. In conclusion, tetracycline exemplifi es how drugs
Non-compartmental PK analysis and statistical analysis showed
with poor absorption have decreased ability to achieve ad-
that all plasma levels were above control (no exposure). Average
equate blood levels when dosed via water.
plasma concentration levels for the 125- and 250-ppm groups
were not signifi cantly diff erent from one another, but were
1. Mason et al. 2009, J. Anim. Sci., p 3179-3186.
signifi cantly less than the 500-ppm group (Table 1). Population PK analysis showed that for tetracycline, health status did not
2. Dorr et al. 2009, JAVMA, p 299-304.
improve the ability of the model to predict plasma concentra-tions. The population model included body weight, medication and water use. The population model was able to predict plasma concentrations of tetracycline and PK values (Vd, Cl) similar to previously published values. Bio-availability for the population model was similar to oral bioavailability (F) from the in vivo study.
Proceedings of the 21st IPVS Congress, Vancouver, Canada – July 18-21, 2010
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