The plasma kinetic profile of moxidectin (MXD) in ewes during the last third of pregnancy was studied after the subcutaneous dose of 0.2 mg/kg of body weight (bw). Two groups of sheep (n = 7) that were equally balanced in body weight were used. Group I (control) was maintained unmated, while Group II (pregnant) was estrous-synchronized and mated with fertile rams. Both groups were maintained under similar conditions regarding management and feeding. When the ewes from Group II fulfilled 120 days of pregnancy, both groups were treated with a subcutaneous injection of 0.2 mg of MXD/kg bw. Blood samples were collected at different set times between 1 h and 40 days post-treatment. After plasma extraction and derivatization, the samples were analyzed using high-performance liquid chromatography with fluorescence detection. A noncompartmental pharmacokinetic analysis was performed, and the data were compared using Student's t-test. The mean pharmacokinetic parameters, including Cmax , Tmax , and the area under the concentration-time curve (AUC), were similar for both groups of sheep. The average of elimination half-life was significantly lower (P = 0.0023) in the pregnant (11.49 ± 2.2 days) vs. the control (17.89 ± 4.84 days) sheep. Similarly, the mean residence time (MRT) for the pregnant group (20.6 ± 3.8 days) was lower (P = 0.037) than that observed in the control group (27.4 ± 9.1 days). It is concluded that pregnancy produces a significant decrease in mean values of half-life of elimination of MXD, indicating that pregnancy can increase the rate of elimination of the drug reducing their permanence in the body.
1. The purpose of this study was to understand the effects of the acute inflammatory response (AIR) induced by Escherichia coli lipopolysaccharide (LPS) on florfenicol (FFC) and FFC-amine (FFC-a) plasma and tissue concentrations. 2. Ten Suffolk Down sheep, 60.5 ± 4.7 kg, were distributed into two experimental groups: group 1 (LPS) treated with three intravenous doses of 1 μg/kg bw of LPS at 24, 16, and 0.75 h (45 min) before FFC treatment; group 2 (Control) was treated with saline solution (SS) in parallel to group 1. An IM dose of 20 mg FFC/kg was administered at 0.75 h after the last injection of LPS or SS. Blood and tissue samples were taken after FFC administration. 3. The plasma AUC values of FFC were higher (p = 0.0313) in sheep treated with LPS (21.8 ± 2.0 μg·min/mL) compared with the control group (12.8 ± 2.3 μg·min/mL). Lipopolysaccharide injections increased FFC concentrations in kidneys, spleen, and brain. Low levels of plasma FFC-a were observed in control sheep (C = 0.14 ± 0.01 μg/mL) with a metabolite ratio (MR) of 4.0 ± 0.87%. While in the LPS group, C increased slightly (0.25 ± 0.01 μg/mL), and MR decreased to 2.8 ± 0.17%. 4. The changes observed in the plasma and tissue concentrations of FFC were attributed to the pathophysiological effects of LPS on renal hemodynamics that modified tissue distribution and reduced elimination of the drug.
The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2 mg/kg. Ten Suffolk Down sheep, 55 ± 3.3 kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1 μg LPS/kg bw at -24, -16, and -0.75 hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2 mg IVM/kg was administered 45 min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non-compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half-life (2.85 days), mean residence time (MRT) (2.27 days), area under the plasma concentration curve over time (AUC, 117.4 ng day ml ), volume of distribution (875.6 ml/kg), and clearance (187.1 ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E. coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.
Let K be an algebraically closed field of characteristic 0, complete with respect to an ultrametric absolute value. Results on branched values obtained in a previous paper are used to prove that algebraic functional equations of the form g q = hf q + w have no solution among transcendental entire functions f, g or among unbounded analytic functions inside an open disk, when w is a polynomial or a bounded analytic function and h is a polynomial or an analytic function whose zeros are of order multiple of q. We also show that an analytic function whose zeros are multiple of an integer q inside a disk is the q-th power of another analytic function, provided q is prime to the residue characteristic. Let K be an algebraically closed field of characteristic 0, of residue characteristic p, complete with respect to an ultrametric absolute value | • |. Given α ∈ K and R ∈ R * + , we denote by d(α, R) the closed disk {x ∈ K : |x − α| ≤ R} and by d(α, R −) the open disk {x ∈ K : |x − α| < R} contained in K, by A(K) the K-algebra of analytic functions in K (i.e. the set of power series with an infinite radius of convergence) and by M(K) the field of meromorphic functions in K and by K(x) the field of rational functions. In the same way, given α ∈ K and R > 0, we denote by A(d(α, R −)) the K-algebra of analytic functions in d(α, R −) (i.e. the set of power series with a radius of convergence ≥ R) and by M(d(α, R −)) the field of fractions of A(d(α, R −)). We then denote by A b (d(α, R −)) the Kalgebra of bounded analytic functions in d(α, R −) and by M b (d(α, R −)) the field of fractions of A b (d(α, R −)). And we set A u (d(α, R −)) = A(d(α, R −)) \ A b (d(α, R −)) and M u (d(α, R −)) = M(d(α, R −)) \ M b (d(α, R −)). As in complex functions, a meromorphic function is said to be transcendental if it is not a rational function. Then transcendental functions are known to be transcendental on the field K(x) [4]. In complex functions theory, a notion closely linked to Picard's exceptional values [4], [6] was introduced: the notion of "perfectly branched value" [2]. In [5] the same notion was introduced on M(K) and on M u (d(a, R −)). Let us recall these notions. Definition: Let f be a meromorphic function in C (resp. K, resp. d(a, R −)). A value b ∈ C will be called a perfectly branched value for f if all zeros of f − b are of multiple order except finitely many. And b is called a totally branched value for f if all zeros of f − b are of multiple order, without exception.
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