Research

18 pages, 2564 KiB

Open AccessArticle

Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes

by Anxiong Huang, Xiao Huang, Zhihao Zhang, Zonghui Yuan, Lingli Huang, Yulian Wang, Yanfei Tao, Dongmei Chen, Zhenli Liu and Haihong Hao

Pharmaceutics 2022, 14(10), 2058; https://doi.org/10.3390/pharmaceutics14102058 - 27 Sep 2022

Cited by 1 | Viewed by 1187

Abstract

Glaesserella parasuis (G. parasuis) causes Glasser’s disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study [...] Read more.

Glaesserella parasuis (G. parasuis) causes Glasser’s disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study was to recommend the optimal dosing regimen for the treatment of G. parasuis infection which contains resistance and virulence genes by ADP/SMZ compound through pharmacokinetics–pharmacodynamics (PK-PD) modeling. The whole genome of the virulent strain G. parasuis H78 was obtained and annotated by whole genome sequencing. The results show that G. parasuis H78 consists of a unilateral circular chromosome with prophages in the genome. The annotation results of G. parasuis H78 showed that the genome contained a large number of virulence-related genes and drug resistance-related genes. The in vitro PD study showed that the antibacterial effect of ADP/SMZ compound against G. parasuis was time-dependent, and AUC/MIC was selected as the PK-PD modeling parameter. The PK study showed that the content of ADP/SMZ compound in pulmonary epithelial lining fluid (PELF) was higher than plasma, and there were no significant differences in ADP and SMZ PK parameters between the healthy and infected group. The dose equation to calculate the optimal dosing regimen of ADP/SMZ compound administration for control of G. parasuis infection was 5/25 mg/kg b.w., intramuscular injection once a day for 3~5 consecutive days. The results of this study provide novel therapeutic options for the treatment of G. parasuis infection to decrease the prevalence and disease burden caused by G. parasuis. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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10 pages, 1323 KiB

Open AccessArticle

Pharmacokinetics of Bupivacaine Following Administration by an Ultrasound-Guided Transversus Abdominis Plane Block in Cats Undergoing Ovariohysterectomy

by Marta Garbin, Javier Benito, Hélène L. M. Ruel, Ryota Watanabe, Beatriz P. Monteiro, Petra Cagnardi and Paulo V. Steagall

Pharmaceutics 2022, 14(8), 1548; https://doi.org/10.3390/pharmaceutics14081548 - 25 Jul 2022

Cited by 4 | Viewed by 3642

Abstract

Bupivacaine is commonly used for peripheral nerve block in veterinary medicine. This study described the pharmacokinetics of two doses of bupivacaine following administration by an ultrasound-guided transversus abdominis plane (TAP) block in cats undergoing ovariohysterectomy. Twelve healthy female adult cats were included in [...] Read more.

Bupivacaine is commonly used for peripheral nerve block in veterinary medicine. This study described the pharmacokinetics of two doses of bupivacaine following administration by an ultrasound-guided transversus abdominis plane (TAP) block in cats undergoing ovariohysterectomy. Twelve healthy female adult cats were included in a randomized, prospective, blinded clinical trial. Anaesthetic protocol included acepromazine–buprenorphine–propofol–isoflurane–meloxicam. Each cat received 1 mL/kg of bupivacaine 0.2% or 0.25% (BUPI-2 and BUPI-2.5, respectively) via bilateral two-point TAP block before surgery (n = 6/group). Plasma concentrations of bupivacaine were detected using liquid chromatography-mass spectrometry. A one-compartment model and non-compartmental analysis described the pharmacokinetic parameters. Bupivacaine was detected up to 480 min (335 ± 76 in BUPI-2 and 485 ± 198 ng/mL in BUPI-2.5). For BUPI-2 and BUPI-2.5, maximum plasma concentrations were 1166 ± 511 and 1810 ± 536 ng/mL at 33 ± 14 and 47 ± 22 min, clearance was 5.3 ± 1.8 and 4.9 ± 1.5 mL/min/kg, and elimination half-life were 253 ± 55 and 217 ± 52 min, respectively. The two doses of bupivacaine via TAP block produced concentrations below toxic levels in cats. A dose of 2.5 mg/kg bupivacaine was safe to be administered using this block in healthy cats. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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15 pages, 2264 KiB

Open AccessArticle

Optimization of Maduramicin Ammonium-Loaded Nanostructured Lipid Carriers Using Box–Behnken Design for Enhanced Anticoccidial Effect against Eimeria tenella in Broiler Chickens

by Yan Zhang, Runan Zuo, Xinhao Song, Jiahao Gong, Junqi Wang, Mengjuan Lin, Fengzhu Yang, Xingxing Cheng, Xiuge Gao, Lin Peng, Hui Ji, Xia Chen, Shanxiang Jiang and Dawei Guo

Pharmaceutics 2022, 14(7), 1330; https://doi.org/10.3390/pharmaceutics14071330 - 23 Jun 2022

Cited by 6 | Viewed by 1666

Abstract

Maduramicin ammonium (MAD) is one of the most frequently used anticoccidial agents in broiler chickens. However, the high toxicity and low solubility of MAD limit its clinical application. In this study, MAD-loaded nanostructured lipid carriers (MAD–NLCs) were prepared to overcome the defects of [...] Read more.

Maduramicin ammonium (MAD) is one of the most frequently used anticoccidial agents in broiler chickens. However, the high toxicity and low solubility of MAD limit its clinical application. In this study, MAD-loaded nanostructured lipid carriers (MAD–NLCs) were prepared to overcome the defects of MAD by using highly soluble nanostructured lipid carriers (NLCs). The formulation was optimized via a three-level, three-factor Box–Behnken response surface method. Then, the optimal MAD–NLCs were evaluated according to their hydrodynamic diameter (HD), zeta potential (ZP), crystal structure, encapsulation efficiency (EE), drug loading (DL), in vitro release, and anticoccidial effect. The optimal MAD–NLCs had an HD of 153.6 ± 3.044 nm and a ZP of −41.4 ± 1.10 mV. The X-ray diffraction and Fourier-transform infrared spectroscopy results indicated that the MAD was encapsulated in the NLCs in an amorphous state. The EE and DL were 90.49 ± 1.05% and 2.34 ± 0.04%, respectively, which indicated that the MAD was efficiently encapsulated in the NLCs. In the in vitro study, the MAD–NLCs demonstrated a slow and sustained drug release behavior. Notably, MAD–NLCs had an excellent anticoccidial effect against Eimeria tenella in broiler chickens. In summary, MAD–NLCs have huge potential to form a new preparation administered via drinking water with a powerful anticoccidial effect. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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13 pages, 1049 KiB

Open AccessEditor’s ChoiceArticle

Pharmacokinetics of Tildipirosin in Plasma, Milk, and Somatic Cells Following Intravenous, Intramuscular, and Subcutaneous Administration in Dairy Goats

by Juan Sebastián Galecio, Pedro Marín, Verónica Hernandis, María Botía and Elisa Escudero

Pharmaceutics 2022, 14(4), 860; https://doi.org/10.3390/pharmaceutics14040860 - 13 Apr 2022

Cited by 3 | Viewed by 1695

Abstract

Tildipirosin is a macrolide currently authorized for treating respiratory diseases in cattle and swine. The disposition kinetics of tildipirosin in plasma, milk, and somatic cells were investigated in dairy goats. Tildipirosin was administered at a single dose of 2 mg/kg by intravenous (IV) [...] Read more.

Tildipirosin is a macrolide currently authorized for treating respiratory diseases in cattle and swine. The disposition kinetics of tildipirosin in plasma, milk, and somatic cells were investigated in dairy goats. Tildipirosin was administered at a single dose of 2 mg/kg by intravenous (IV) and 4 mg/kg by intramuscular (IM) and subcutaneous (SC) routes. Concentrations of tildipirosin were determined by an HPLC method with UV detection. Pharmacokinetic parameters were estimated by non-compartmental analysis. Muscle damage, cardiotoxicity, and inflammation were evaluated. After IV administration, the apparent volume of distribution in the steady state was 7.2 L/kg and clearance 0.64 L/h/kg. Plasma and milk half-lives were 6.2 and 58.3 h, respectively, indicating nine times longer persistence of tildipirosin in milk than in plasma. Moreover, if somatic cells are considered, persistence and exposure measured by the area under concentration–time curve (AUC) significantly exceeded those obtained in plasma. Similarly, longer half-lives in whole milk and somatic cells compared to plasma were observed after IM and SC administration. No adverse effects were observed. In brief, tildipirosin should be reserved for cases where other suitable antibiotics have been unsuccessful, discarding milk production of treated animals for at least 45 days or treating goats at the dry-off period. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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13 pages, 1120 KiB

Open AccessArticle

Comparative Pharmacokinetics of Sulfadiazine and Its Metabolite N4-Acetyl Sulfadiazine in Grass Carp (Ctenopharyngodon idella) at Different Temperatures after Oral Administration

by Ning Xu, Miao Li, Zhoumeng Lin and Xiaohui Ai

Pharmaceutics 2022, 14(4), 712; https://doi.org/10.3390/pharmaceutics14040712 - 26 Mar 2022

Cited by 6 | Viewed by 1640

Abstract

In this study, the plasma pharmacokinetics and tissue disposition of sulfadiazine (SDZ) and its main metabolite, N₄-acetyl sulfadiazine (ACT-SDZ), were compared between 18 and 24 °C following a single oral administration of SDZ at 50 mg/kg in grass carp (Ctenopharyngodon [...] Read more.

In this study, the plasma pharmacokinetics and tissue disposition of sulfadiazine (SDZ) and its main metabolite, N₄-acetyl sulfadiazine (ACT-SDZ), were compared between 18 and 24 °C following a single oral administration of SDZ at 50 mg/kg in grass carp (Ctenopharyngodon idella). The plasma and tissues were sampled from 0.167 h up to 96 h and analyzed by ultra-performance liquid chromatography with an ultraviolet detector. The pharmacokinetic parameters were estimated using a one-compartmental approach. Results showed that pharmacokinetics of SDZ and ACT-SDZ in plasma and tissues were notably influenced by the increase of temperature. The increased temperature shortened the absorption half-life (K01_HL) of SDZ and ACT-SDZ in gill, kidney, and plasma, but increased in liver and muscle + skin. The elimination half-life (K10_HF) and the area under concentration-time curve (AUC_0–∞) of SDZ and ACT-SDZ all presented a declined trend. The apparent volume of distribution (V_F) of SDZ in plasma was increased from 0.93 to 1.64 L/kg, and the apparent systemic total body clearance (Cl_F) was also increased from 0.01 to 0.05 L/h/kg. Overall, the rise of temperature decreased K10_HF, AUC_0–∞ of SDZ, and ACT-SDZ in plasma and tissues, but increased V_F and Cl_F in the plasma for SDZ. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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12 pages, 1348 KiB

Open AccessArticle

Synovial and Systemic Pharmacokinetics of Florfenicol and PK/PD Integration against Streptococcus suis in Pigs

by Zoltán Somogyi, Patrik Mag, Dóra Kovács, Ádám Kerek, Pál Szabó, László Makrai and Ákos Jerzsele

Pharmaceutics 2022, 14(1), 109; https://doi.org/10.3390/pharmaceutics14010109 - 03 Jan 2022

Cited by 11 | Viewed by 2115

Abstract

Florfenicol is a member of the phenicol group, a broad-spectrum antibacterial agent. It has been used for a long time in veterinary medicine, but there are some factors regarding its pharmacokinetic characteristics that have yet to be elucidated. The aim of our study [...] Read more.

Florfenicol is a member of the phenicol group, a broad-spectrum antibacterial agent. It has been used for a long time in veterinary medicine, but there are some factors regarding its pharmacokinetic characteristics that have yet to be elucidated. The aim of our study was to describe the pharmacokinetic profile of florfenicol in synovial fluid and plasma of swine after intramuscular (i.m.) administration. In addition, the dosage regimen of treatment of arthritis caused by S. suis was computed for florfenicol using pharmacokinetic/pharmacodynamic (PK/PD) indices. As the first part of our investigation, the pharmacokinetic (PK) parameters of florfenicol were determined in the plasma and synovial fluid of six pigs. Following drug administration (15 mg/kg_bw, intramuscularly), blood was drawn at the following times: 10, 20, 30, 40, 50 and 60 min, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48 and 72 h; synovial fluid samples were taken after 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h. The concentration of florfenicol was determined by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method via multiple reaction monitoring (MRM) modes. As the second part of our research, minimum inhibitory concentration (MIC) values of florfenicol were determined in 45 S. suis strains isolated from clinical samples collected in Hungary. Furthermore, a strain of S. suis serotype 2 (SS3) was selected, and killing-time curves of different florfenicol concentrations (0.5 µg/mL, 1 µg/mL and 2 µg/mL) were determined against this strain. Peak concentration of the florfenicol was 3.58 ± 1.51 µg/mL in plasma after 1.64 ± 1.74 h, while it was 2.73 ± 1.2 µg/mL in synovial fluid 3.4 ± 1.67 h after administration. The half-life in plasma was found to be 17.24 ± 9.35 h, while in synovial fluid it was 21.01 ± 13.19 h. The area under the curve (AUC_24h) value was 54.66 ± 23.34 μg/mL·h for 24 h in plasma and 31.24 ± 6.82 μg/mL·h for 24 h in synovial fluid. The drug clearance scaled by bioavailability (Cl/F) in plasma and synovial fluid was 0.19 ± 0.08 L/h/kg and 0.29 ± 0.08 L/h/kg, respectively. The mean residence time (MRT) in plasma and synovial fluid was 24.0 ± 13.59 h and 27.39 ± 17.16 h, respectively. The steady-state volume of distribution (V_ss) in plasma was calculated from Cl/F of 0.19 ± 0.08 L/h/kg, multiplied by MRT of 24.0 ± 13.59 h. For the PK/PD integration, average plasma and synovial fluid concentration of florfenicol was used in a steady-state condition. The obtained MIC₅₀ value of the strains was 2.0 µg/mL, and MIC₉₀ proved to be 16.0 µg/mL. PK/PD integration was performed considering AUC_24h/MIC breakpoints that have already been described. This study is the first presentation of the pharmacokinetic behavior of florfenicol in swine synovia as well as a recommendation of extrapolated critical MICs of S. suis for therapeutic success in the treatment of S. suis arthritis in swine, but it should be noted that this requires a different dosage regimen to that used in authorized florfenicol formulations. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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14 pages, 1047 KiB

Open AccessArticle

Disposition of Cefquinome in Turkeys (Meleagris gallopavo) Following Intravenous and Intramuscular Administration

by Mohamed Elbadawy, Ahmed Soliman, Amira Abugomaa, Adel Alkhedaide, Mohamed Mohamed Soliman and Mohamed Aboubakr

Pharmaceutics 2021, 13(11), 1804; https://doi.org/10.3390/pharmaceutics13111804 - 28 Oct 2021

Cited by 3 | Viewed by 1612

Abstract

The bioavailability and pharmacokinetics in turkeys of cefquinome (CFQ), a broad-spectrum 4th-generation cephalosporin antibiotic, were explored after a single injection of 2 mg/kg body weight by intravenous (IV) and intramuscular (IM) routes. In a crossover design and 3-weeks washout interval, seven turkeys were [...] Read more.

The bioavailability and pharmacokinetics in turkeys of cefquinome (CFQ), a broad-spectrum 4th-generation cephalosporin antibiotic, were explored after a single injection of 2 mg/kg body weight by intravenous (IV) and intramuscular (IM) routes. In a crossover design and 3-weeks washout interval, seven turkeys were assigned for this objective. Blood samples were collected prior to and at various time intervals following each administration. The concentration of CFQ in plasma was measured using HPLC with a UV detector set at 266 nm. For pharmacokinetic analysis, non-compartmental methods have been applied. Following IV administration, the elimination half-life (t_1/2ʎz), distribution volume at steady state (Vd_ss), and total body clearance (Cl_tot) of CFQ were 1.55 h, 0.54 L/kg, and 0.32 L/h/kg, respectively. Following the IM administration, CFQ was speedily absorbed with an absorption half-life (t_1/2ab) of 0.25 h, a maximum plasma concentration (C_max) of 2.71 μg/mL, attained (T_max) at 0.56 h. The bioavailability (F) and in vitro plasma protein binding of CFQ were 95.56% and 11.5%, respectively. Results indicated that CFQ was speedily absorbed with a considerable bioavailability after IM administration. In conclusion, CFQ has a favorable disposition in turkeys that can guide to estimate optimum dosage regimes and eventually lead to its usage to eradicate turkey’s susceptible bacterial infections. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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12 pages, 1657 KiB

Open AccessArticle

The Anti-Nociceptive Potential of Tulathromycin against Chemically and Thermally Induced Pain in Mice

by Mohamed Elbadawy, Amira Abugomaa, Hussein M. El-Husseiny, Ahmed S. Mandour, Mohamed M. Abdel-Daim, Salama Mostafa Aboelenin, Mohamed Mohamed Soliman and Amany El-Mleeh

Pharmaceutics 2021, 13(8), 1247; https://doi.org/10.3390/pharmaceutics13081247 - 12 Aug 2021

Cited by 4 | Viewed by 2619

Abstract

The present study was conducted to evaluate the analgesic potential of the new triamilide macrolide antibiotic, tulathromycin, at 20 and 40 mg/kg of body weight (BW), subcutaneously against acute pain in mice. Acute pain was induced either chemically (using acetic acid-induced writhing and [...] Read more.

The present study was conducted to evaluate the analgesic potential of the new triamilide macrolide antibiotic, tulathromycin, at 20 and 40 mg/kg of body weight (BW), subcutaneously against acute pain in mice. Acute pain was induced either chemically (using acetic acid-induced writhing and formalin-induced pain tests) or thermally (using hot-plate, and tail-flick tests). In the acetic acid-induced writhing test, tulathromycin induced a dose-dependent and significant decrease in the number of writhes compared with the control group. In the late phase of the formalin test, a significant decline in hind paw licking time compared with the control group was observed. In the hot-plate and tail-flick tests, tulathromycin caused a dose-dependent and significant prolongation of latency of nociceptive response to heat stimuli, compared with the control group. These findings may indicate that tulathromycin possesses significant peripheral and central analgesic potentials that may be valuable in symptomatic relief of pain, in addition to its well-established antibacterial effect. Full article

(This article belongs to the Special Issue Specific Drug Disposition in Veterinary Medicine)

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