Integration of pharmacokinetic–pharmacodynamic for dose optimization of doxycycline against Haemophilus parasuis in pigs          下载免费PDF全文

Y. Wang  A. Sajid  S. Ahmed  X. Li 《Journal of veterinary pharmacology and therapeutics》2018,41(5):706-718

The aims of this study were to establish optimal doses of doxycycline (dox) against Haemophilus parasuis on the basis of pharmacokinetic–pharmacodynamic (PK‐PD) integration modeling. The infected model was established by intranasal inoculation of organism in pigs and confirmed by clinical signs, blood biochemistry, and microscopic examinations. The recommended dose (20 mg/kg b.w.) was administered in pigs through intramuscular routes for PK studies. The area under the concentration 0‐ to 24‐hr curve (AUC_0–24), elimination half‐life (T_½ke), and mean residence time (MRT) of dox in healthy and H. parasuis‐infected pigs were 55.51 ± 5.72 versus 57.10 ± 4.89 μg·hr/ml, 8.28 ± 0.91 versus 9.80 ± 2.38 hr, and 8.43 ± 0.27 versus 8.79 ± 0.18 hr, respectively. The minimal inhibitory concentration (MIC) of dox against 40 H. parasuis isolates was conducted through broth microdilution method, the corresponding MIC₅₀ and MIC₉₀ were 0.25 and 1 μg/ml, respectively. The Ex vivo growth inhibition data suggested that dox exhibited a concentration‐dependent killing mechanism. Based on the observed AUC_24 hr/MIC values by modeling PK‐PD data in H. parasuis‐infected pigs, the doses predicted to obtain bacteriostatic, bactericidal, and elimination effects for H. parasuis over 24 hr were 5.25, 8.55, and 10.37 mg/kg for the 50% target attainment rate (TAR), and 7.26, 13.82, and 18.17 mg/kg for 90% TAR, respectively. This study provided a more optimized alternative for clinical use and demonstrated that the dosage 20 mg/kg of dox by intramuscular administration could have an effective bactericidal activity against H. parasuis.  相似文献   

Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows          下载免费PDF全文

M. Ballent  P. Viviani  F. Imperiale  P. Dominguez  S. Halwachs  H. Mahnke  W. Honscha  C. Lanusse  G. Virkel  A. Lifschitz 《Journal of veterinary pharmacology and therapeutics》2018,41(2):292-300

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO₂) into milk. The goal of this study was to evaluate the presence of potential in vivo drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO₂ was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO₂ into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO₂ were not modified in the presence of OFZ. The pattern of MNPSO₂ excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO₂) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO₂) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the in vivo pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO₂.  相似文献   

In vitro evaluation of a simulated pneumoperitoneum environment using carbon dioxide on canine transitional cell carcinoma          下载免费PDF全文

Rashi Asthana MSc  Michelle L. Oblak DVM  DVSc  Diplomate ACVS  ACVS Fellow of Surgical Oncology  Ameet Singh DVM  DVSc  Diplomate ACVS 《Veterinary surgery : VS》2018,47(3):412-420

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Pharmacokinetics of cefquinome in healthy and Pasteurella multocida‐infected rabbits          下载免费PDF全文

S. T. Elazab  D. E. Schrunk  R. W. Griffith  S. M. Ensley  G. Dell'Anna  K. Mullin  M. G. Elsayed  M. S. Amer  S. M. El‐Nabtity  W. H. Hsu 《Journal of veterinary pharmacology and therapeutics》2018,41(3):374-377

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida‐infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0–2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1–2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high‐performance liquid chromatography. The values of elimination half‐life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*μg/ml, 3.63 hr* hr*μg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*μg/ml, 9.85 hr* hr*μg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida‐infected rabbits.  相似文献   

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows          下载免费PDF全文

M. D. Kleinhenz  P. J. Gorden  J. S. Smith  J. A. Schleining  K. E. Kleinhenz  L. L. Wulf  P. K. Sidhu  D. Rea  J. F. Coetzee 《Journal of veterinary pharmacology and therapeutics》2018,41(3):490-493

A transdermal formulation of the nonsteroidal anti‐inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single‐dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high‐pressure liquid chromatography with mass spectroscopy (HPLC ‐MS ). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (T max) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half‐life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg^?1, and volume of distribution of fraction (V z/F ) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses.  相似文献   

Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats          下载免费PDF全文

William Buhles  Jessica M. Quimby  Daizie Labelle  Valentine S. Williams 《Journal of veterinary pharmacology and therapeutics》2018,41(5):644-651

Single and multiple dose pharmacokinetics (PK) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross‐over single dose study (n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study (n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean T_max = 15.9 hr, C_max = 21.5 ng/mL, AUC_0‐24 = 100 ng*hr/mL, AUC_0‐∞ = 260 ng*hr/mL and calculated half‐life = 26.8 hr. Single oral administration of mirtazapine resulted in mean T_max = 1.1 hr, C_max = 83.1 ng/mL, AUC_0‐24 = 377 ng*hr/mL, AUC_0‐∞ = 434 ng*hr/mL and calculated half‐life = 10.1 hr. Mean relative bioavailability (F) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean T_max = 2.1 hr, C_max = 39.6 ng/mL, AUC_0‐24 = 400 ng*hr/mL, AUC_0‐∞ = 647 ng*hr/mL and calculated half‐life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.  相似文献   

CD117‐ and vimentin‐positive telocytes in the bovine teat sphincter          下载免费PDF全文

M. G. Wagener  S. Leonhard‐Marek  J.‐D. Häger  C. Pfarrer 《Anatomia, histologia, embryologia》2018,47(3):268-270

Mastitis is a common economically relevant problem in dairy farming. As the major entry for pathogens is the papillary duct, one of the first defence mechanisms is the teat sphincter. This sphincter shows a rhythmic contractility of yet unknown origin. Searching for possible modulatory pacemaker cells, teat sphincters of eight cows were stained immunohistochemically with antibodies against CD117 and vimentin and evaluated microscopically for the presence of telocytes. CD117‐ and vimentin‐positive telocytes with telopodes were found in close contact with smooth muscle cells. Our findings present a first evidence of telocytes in the teat of bovines.  相似文献   

Macro‐anatomical and morphometric studies of the hindlimb of grasscutter (Thryonomys swinderianus,Temminck‐1827)          下载免费PDF全文

K. T. Onwuama  S. A. Ojo  J. O. Hambolu  T. Dzenda  F. O. Zakari  S. O. Salami 《Anatomia, histologia, embryologia》2018,47(1):21-27

The hindlimb of the grasscutter (Thryonomys swinderianus, Temminck‐1827) was studied using 12 adult (≥6 months) rats of either sex with the mean weights of 1.42 ± 0.20 kg and 0.82 ± 0.13 kg for buck (n = 6) and doe (n = 6), respectively (p < .05). Characteristics of the bones were studied by gross observation after their preparation. Measurements of different segments of the hindlimb were also taken, giving a total average length of 31.80 cm. Correlation coefficients between length of bone and weight of rats were positive (p < .05) in bucks for all bone segments, except the pes (p > .05), whereas those in does were all non‐significant (p > .05), with significant sexual dimorphism in the relationships. The average total number of bones in the hindlimb was 92, with no apparent sexual dimorphism. The bones of the hindlimb revealed important differences and similarities in morphology with those of other rodents. The Os coxae presented a relatively large obturator foramen, formed by the ramus of the ischium and shaft of the pubis. The femur had a body and two extremities with a prominent head, well‐defined neck and trochanter. The fibula, a slender bone with triangular‐shaped proximal extremity, ran down the length of tibia with proximal attachment (via cartilage) and distal fusion, leaving an extensive interosseus space. The pes revealed eight tarsals and four metatarsals; each of the metatarsals showed three phalanges.  相似文献   

Categorization of the pelvic limb standing posture in nine breeds of dogs          下载免费PDF全文

S. S. Sabanci  M. K. Ocal 《Anatomia, histologia, embryologia》2018,47(1):58-63

The objective of the study was to categorize objectively nine breeds of healthy dogs according to pelvic limb standing posture. A total of 135 dogs from different breeds were used and the standing angles of the hip, stifle, and tarsal joints, together with the percentages of the greater trochanter, patella and tuber calcanei heights, with respect to crista iliaca height, were used as discriminant variables for the categorization of pelvic limb posture. All included breeds were allocated to three groups of the standing pelvic limb posture. The best discriminant variables between the three groups were the percentage of patellar height, and the standing angles of the stifle and tarsal joints. German shepherds, Anatolian shepherds, golden retrievers, Rottweilers, Belgian Malinois and Dobermann pinschers were well separated between 89% and 100% success rate for the categorization. The minimal success rate was determined in Berner sennenhunds as the ratio of 75%. It was also determined that Dobermann pinschers had the straightest pelvic limbs, while German shepherds had the most angulated pelvic limbs. Further studies are required to document the impact of postural differences in active and passive structure diseases of the locomotor system of the pelvic limb among dog breeds.  相似文献   

What is your diagnosis? Caudal fossa mass from a dog          下载免费PDF全文

Shannon Jones Hostetter  Hilary Z. Hu  Joseph S. Haynes 《Veterinary clinical pathology / American Society for Veterinary Clinical Pathology》2018,47(2):322-323

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