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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.

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The transplacental exchange of moxidectin after maternal or fetal intravenous (i.v.) administration was studied using the chronically catheterized fetal sheep model. Nine pregnant Suffolk Down sheep of 65.7 +/- 5.9 kg body weight (bw) were surgically prepared to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. The ewes were randomly assigned to two experimental groups. In group 1 (maternal injection) five ewes were treated with an i.v. bolus of 0.2 mg of moxidectin/kg bw. In group 2, (fetal injection) an i.v. bolus of 1 mg of moxidectin was administered to the four fetuses by femoral vein catheters. Maternal and fetal blood and amniotic fluid samples were taken before and after moxidectin administration for a 144 h post-treatment period. Samples were analyzed by liquid chromatography. A noncompartmental pharmacokinetic analysis was performed and statistical differences were determined by mean of parametric and nonparametric statistical tests. Pharmacokinetic differences observed in maternal variables were shorter elimination half-life and mean residence time compared with values previously reported for ivermectin. Drug diffusion from maternal to fetal circulation (AUC(0-t) = 232.6 +/- 72.5 ng.h/mL) was statistically not different (P = 0.09) compared with fetal to maternal diffusion (AUC(0-t) = 158.0 +/- 21.6 ng.h/mL). Fetuses showed significantly (P = 0.008) lower drug body clearance values compared with those observed in the maternal side. Considering the observed transplacental passages between materno-fetal or feto-maternal circulations, we conclude that the placental barrier is not effective in preventing the moxidectin diffusion between mother and fetus.

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In pregnant sheep at 120-130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 +/- 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t((1/2)beta)). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 +/- 0.6 ng/mL) and AUC (89.1 +/- 11.4 ng.h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 +/- 177.9 mL/kg) and lower values of t((1/2)beta) (8.0 +/- 1.4 h) and mean residence time (8.0 +/- 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment.

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The plasma kinetic profile of ivermectin during the last trimester of pregnancy was studied in ewes after a single subcutaneous administration of 0.2 mg/kg body weight (BW). Sheep were randomly distributed into two groups. Ewes in group 1 (control, n=6) were left unmated, whereas in group 2 (pregnant, n=6) ewes were estrus-synchronized and mated with rams. Both groups were housed under similar conditions of management and feeding. At 120 days of pregnancy, both groups were given a subcutaneous injection of 0.2 mg/kg BW of ivermectin. Blood samples were taken by jugular puncture according to a fixed protocol between 1 h and 40 days post-treatment. After plasma extraction and derivatization, samples were analyzed by high performance liquid chromatography with fluorescence detection. A computerized pharmacokinetic analysis was performed, and the data were compared by means of the Student t-test. The results showed that plasma concentrations of ivermectin remained longer in the pregnant than in the control group. The mean values of pharmacokinetic parameters C(max), t(max), and area under the concentration-time curve (AUC) were similar for both groups of sheep. The mean residence time (MRT) values for the pregnant group (8.8+/-1.4 days) were higher (P<0.05) than those observed in the control group (5.3+/-1.9 days). It can be concluded that pregnancy increases the residence time of ivermectin in the plasma of pregnant sheep when it is administered subcutaneously.

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To determine clinical and epidemiological features of scorpion stings in two departments of Colombia, a descriptive study was performed in the hospitals of 10 towns from Antioquia (2 256 071 inhabitants) and five from Tolima (630 424 inhabitants). One hundred and twenty-nine cases were admitted during one year, 51 in Antioquia, 78 in Tolima and 41 were children less than 15 years old. Most stings (70.5%) occurred inside the house; 27.9% were on the hands and 26.4% on the feet. The scorpion species involved were Tityus pachyurus (51), Centruroides gracilis (31), T. fuehrmanni (29), T. asthenes (7) and Chactas spp. (1). In 10 cases the scorpion involved was not identified. Systemic envenoming signs (e.g. vomiting, tachypnea) were significantly more frequent in children than in adults (P < 0.05). Four children had hypertension, but none developed pulmonary oedema. One 3-year-old girl, stung by T. asthenes, had acute oedematous pancreatitis. Ninety-eight patients had mild envenoming. Moderate (27 patients) and severe (four patients) envenoming was significantly more frequent in children than in adults (P = 0.003; relative risk = 2.97). A pepsin-digested anti-Centruroides spp. antivenom was administered to 19 of 31 patients presenting systemic envenoming signs. No adverse reactions to antivenom were observed.

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