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Amaç: Bu çalışmada süt ineklerinde klinik endometritisin tedavisi ve gebelik oranı üzerine N-asetilsistein (NAS)’in etkisinin belirlenmesi amaçlandı. Gereç ve Yöntem: Çalışma, ticari bir süt işletmesinde 50-60 günlük gönüllü bekleme süresinden sonra endometritisin klinik bulgularını gösteren 36 inek üzerinde gerçekleştirildi. Klinik endometritis, vajinada belirlenen uterus akıntısının değerlendirilmesiyle tanımlandı. İneklerden servikal svap örnekleri mikroorganizma ve tedavi için en etkili antibakteriyel ajanı belirlemek için toplandı. İnekler rastgele NAS tedavisi yapılan (NAS-T) ve yapılmayan (nNAS-T) olmak üzere iki gruba ayrıldı. NAS-T grubuna (n=18) %2’lik NAS uygulamasından 12 saat sonra amoksisilin trihidrat+potasyum klavulanat (3500 mg+875 mg) uygulaması yapıldı ve bu uygulama üç gün tekrar edildi. nNAS-T grubuna (n=18), NAS-T grubunda uygulanan tedavi protokolündeki NAS uygulaması yerine 100 mL serum fizyolojik uygulaması yapıldı. Tedavi oranı, tedaviyi takiben gerçekleşen ilk doğal östrusta klinik endometritisin bulgularını göstermeyen (vaginal muayenede şeffaf veya yarı şeffaf mukus) ineklerin oranı olarak tanımlandı. Hayvanlar tedaviden sonraki ilk doğal östrusta suni yolla tohumlandı. Bulgular: NAS-T grubunda tedavi (%83.3) ve gebelik (%66.7) oranlarının nNAS-T grubuna (sırasıyla %55.5 ve %27.8) göre önemli derecede yüksek olduğu belirlendi (P, Aim: The objective of this study was to investigate the effect of N-acetylcysteine (NAC) on the treatment of the clinical endometritis and pregnancy rate in dairy cows. Materials and Methods: This study was performed on 36 cows with clinical signs of endometritis after VWP (voluntary waiting period, 50-60 days) on a commercial dairy farm. The clinical endometritis was diagnosed by evaluation of uterine discharge detected in the vagina. Cervical swab samples were collected to determine microorganism and the most effective antibacterial agent for the treatment. Cows were randomly allocated to NAC treatment (NAC-T) and non-NAC treatment (nNAC-T) groups. The NAC-T group (n=18) received an intrauterine infusion of amoxicillin trihydrate+potassium clavulanate (3500 mg+875 mg) in 100 mL dosages after 12 hours of an intrauterine infusion of 2% NAC during three days. Saline (total volume 100 mL) to the nNAC-T group (n=18) was given instead of NAC in the same protocol of the NAC-T group. The clinical cure rate was described as the percentage of cows with no signs of clinical endometritis (the clear or translucent mucus at vaginal examination), at the examination in first natural estrus following treatment. Animals were artificially inseminated following the first natural estrus after treatment. Results: The clinical cure (83.3%) and pregnancy rates (66.7%) in the NAC-T group were significantly higher than those (55.5% and 27.8%, respectively) of nNAC-T group (P

Enrofloxacin (ENR) rapidly localizes in eukaryotic cells in vitro but does not remain for prolonged periods, thereby reducing the ENR efficacy of defense against intracellular pathogens. Delivery of ENR in a liposome-encapsulated form may enhance its intracellular residence time. In this study, experimental pneumonia was induced in healthy and dexamethasone-treated rats using Klebsiella pneumoniae serotype II. Free and liposome-encapsulated ENR were injected intravenously into the infected animals at a dose of 7.5 mg/kg/day for 5 days. Samples of tissue, plasma and bronchoalveolar lavage (BAL) fluid were obtained at 1, 2, 3 and 4 days and 1, 2, 3 and 4 weeks after the first antibiotic treatment. All of the samples were evaluated cytologically, enzymologically, microbiologically and pathologically. It was determined that cytologic and enzymologic diagnoses of BAL fluid are not meaningful for evaluating the treatment of the experimental pneumonia in rats. However, it was established that the use of ENR in liposomal form at a dose of 7.5 mg/kg for 5 days is more effective than the free form both in the treatment of K. pneumoniae infections and in the prevention of recurrent infections. Liposome-encapsulated antimicrobial agents should provide another choice for antimicrobial therapy in the future, but further investigation must be completed before clinical use.

Amaç: Prob ilaç olarak kafein (KF) kullanılarak Morkaraman (MK), Akkaraman (AK) ve Anadolu Merinosu (AM) koyun ırklarında in vivo CYP1A2 enzim aktivitesini karşılaştırmak ve pratikte CYP1A2 aktivitesini belirlemede plazma metabolik oranlarının (MO) geçerliliğini ortaya koymaktır.Gereç ve Yöntem: Kafein tüm koyunlara 5 mg/kg dozda damar içi yolla uygulandı. Plazma KF ve paraksantin (PK) düzeyleri yüksek performanslı sıvı kromatografi kullanılarak ölçüldü. CYP1A2 fenotipi PK ve KF’nin plazma konsantrasyon-zaman eğrisinin altındaki alanlar (EAA) arasındaki oran [(PK/KF)ra 3-16. saatlerde PK ve KF’nin plazma konsantrasyonları arasındaki oranlar [(PK/KF)dü. Pratikte tek bir kan örneği üzerinden CYP1A2 fenotipini araştırmak için (PK/KF)arasındaki ilişkiler belirlendi. Öneri: Koyunda plazma (PX/KF)MO→10 h oranı CYP1A2 fenotipinin belirlenmesinde hızlı ve basit bir test olarak kullanılabilir. Ancak, bu çalışmanın sonuçlarına göre CYP1A2 enziminin MK, AK ve AM koyun ırkları arasında substratı durumundaki ilaç ve çevresel bileşiklerin etkilerinde görülenfarklılıklarda klinik yönden öneminin olmayabileceği anlaşılmaktadır., Aim: The aims of this study were to determine the validity of the plasma metabolic ratios (MR) to investigate the CYP1A2 activity in practice and to compare in vivo CYP1A2 enzyme activity using caffeine (CF) as a probe in Morkaraman (MK), Akkaraman (AK) and Anatolia Merino (AM) sheep breeds.Materials and Methods: Caffeine was administered as a single dose of 5 mg/kg b.w. by the intravenous in MK, AK and AM sheep breeds. The plasma levels of CF and paraxanthine (PX) were measured using high-performance liquid chromatography. CYP1A2 phenotyping was measured using the ratio [(PX/CF)concentration-time curve (AUCs) of PX and CF and the ratios [(PX/CF)PX and CF at 3 to 16 h after CF administration. Correlations between the plasma (PX/CF)were determined to investigate of the CYP1A2 phenotyping by single blood sampling in practice.

Amaç: Lipopolisakkaritle (LPS) oluşturulan deneysel endotoksemide sitokinler, adenozin deaminaz (ADA) ve 13,14-dihidro-15-keto-prostaglandin F2α (PGM)’nın kinetik değerlerine tek başlarına ve/veya kombine uygulanan enrofloksasin (ENR), fluniksin meglumin (FM) ve deksametazonun (DEX) etkilerini belirlemektir. Gereç ve Yöntem: Araştırmada kullanılan ratlar 7 gruba ayrıldı. Deneysel endotoksemi oluşturmak için pozitif kontrol grubu dahil bütün gruplara LPS uygulandı. Diğer altı gruba ENR, FM, düşük doz DEX, yüksek doz DEX, ENR+FM+düşük doz DEX ve ENR+FM+yüksek doz DEX uygulandı. Uygulama sonrası 0, 1, 2, 4, 6, 8, 12, 24 ve 48. saatlerde kan örnekleri toplandı. Tümör nekroz faktör alfa (TNFα), interlökin-6 (IL6), interlökin-10 (IL-10), ADA ve PGM düzeyleri ELISA ile belirlendi. Eğri altında kalan alan farmakokinetik programla, plazma veya serum maksimum konsantrasyon (Cmax) ile maksimum konsantrasyona ulaşma zamanı (tmax) direk bakı yöntemiyle belirlendi. Bulgular: Pozitif kontrol (LPS) grubuyla kıyaslandığında EAA0-48 değerlerinin; ENR grubunda PGM için artarken (p, Aim: The objective of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on kinetic values of cytokines, adenosine deaminase (ADA) and 13,14-dihydro-15-keto-prostaglandin F2a (PGM) in lipopolysaccharide-induced endotoxemia. Materials and Methods: Rats were divided into seven groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The six other groups received the following drugs: ENR, FM, low-dose DEX, high-dose DEX, ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24, and 48 hours. Serum tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), interleukin-10 (IL-10), ADA and plasma PGM levels were determined by ELISA. Area under the concentration time curve , maximal concentration in plasma or serum (Cmax) and time to reach (tmax) values were determined by pharmacokinetic computer program. Results: ENR increased (p

WOS: 000486506600001, PubMed: 31183888, The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co-administered to dogs after oral treatment. Twelve healthy cross-bred dogs (weighing 18-21 kg, aged 1-3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15-day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high-performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone-administration were as follows: elimination half-life (t(1/2 lambda z)) 110 +/- 11.06 hr, area under the plasma concentration-time curve (AUC(0-infinity)) 7,805 +/- 1,768 hr(.)ng/ml, maximum concentration (C-max) 137 +/- 48.09 ng/ml, and time to reach C-max (T-max) 14.0 +/- 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone-administration were as follows: t(1/2 lambda z) 7.39 +/- 3.86 hr, AUC(0-infinity) 4,301 +/- 1,253 hr(.)ng/ml, C-max 897 +/- 245 ng/ml, and T-max 5.33 +/- 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except T-max of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.

WOS: 000501034000011, PubMed: 30933367, The pharmacokinetics and bioavailability of levamisole were determined in red-eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three-way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high-performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half-life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr(-1) kg(-1) and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 mu g/ml, respectively, with 0.5 hr of T-max. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t(1/2z), can be recommended as an effective way for treating nematodes in turtles.

WOS: 000501034000010, PubMed: 30719732, The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 +/- 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC-UV method. Pharmacokinetic parameters were calculated using non-compartmental methods. The elimination half-life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 +/- 11.54%. The area under the curve (AUC(0-infinity)) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is, The Coordination Unit of Scientific Research Projects, University of Selcuk, Turkey [15401151]

WOS: 000452969500033, Ceftriaxone (CTX) is a third-generation cephalosporin that has proven to be effective in the treatment of infections caused by a wide range of gram-positive and gram-negative microorganisms. This study aimed to determine the plasma and muscle pharmacokinetics of CTX after its administration via the intravenous (IV) and intramuscular (IM) routes to brown trout (Salmo trutta fario) at temperatures of 10 degrees C-13 degrees C. In total, 140 healthy brown trout (body weight, 245 +/- 38 g) were used. The brown trout received single IV and IM injections of CTX at 25 mg/kg. The IV doses were injected into the caudal vein, whereas the IM doses were injected into the right epaxial muscles. The plasma and muscle tissue concentrations of CTX were measured using high-performance liquid chromatography. Pharmacokinetic parameters were calculated using noncompartmental methods. Following the IV administration of CTX, the elimination half-life (t1/2(sic)z), volume of distribution at steady state, total body clearance, and area under the concentration-time curve (AUC0-72) in plasma were 5.83 h, 0.09 L/kg, 0.02 L/h/kg, and 1079.46 h*mu g/mL, respectively. After the IM administration of CTX, plasma t1/2(sic)z, peak plasma concentration (Cmax), time to reach Cmax, and bioavailability were 22.78 h, 87.92 mu g/mL, 0.5 h, and 27.19%, respectively. The AUCmuscle/AHCplasma ratio following the IV administration was 0.02 and that following the IM administration was 0.04. CTX exhibited low bioavailability and prolonged t1/2(sic)z after the IM administration. The prolonged t1/2(sic)z of CTX could thus be beneficial in brown trout. Nevertheless, future studies that aim to determine the clinical efficacy and pharmacokinetics after repeated administration of CTX are warranted., Coordination of Scientific Research Projects, University of Selcuk, Turkey [16401134], This work was supported by the Coordination of Scientific Research Projects, University of Selcuk, Turkey (project No. 16401134).

WOS: 000460077600009, PubMed: 30474236, The aim of the present study was to determine the pharmacokinetics (PKs) and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 +/- 45 g were used for the investigation. The study was performed in a crossover design (2 x 2 x 2 x 2) with a 15-day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed-phase high-performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were observed in any of the chukar partridges. The mean elimination half-life ranged between 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO administrations were 8.05, 9.58, and 3.39 mu g/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady-state following IV administration were 0.13 L hr(-1) kg(-1) and 0.96 L/kg, respectively. These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.

WOS: 000509740400015, PubMed: 31985285, OBJECTIVE To evaluate the usefulness of intestinal biomarkers in determining the presence of intestinal epithelial damage in neonatal calves with diarrhea caused by 4 etiologic agents. ANIMALS 40 neonatal calves that were healthy (n = 10) or had diarrhea (30). PROCEDURES The study was a cross-sectional study. Results of hematologic analyses and serum concentrations of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), trefoil factor 3 (TFF-3), Claudin-3 (CLDN-3), gamma-enteric smooth muscle actin (ACTG2), intestinal alkaline phosphatase (IAP), interleukin-8 (IL-8), platelet-activating factor (PAF), and leptin (LP) were compared among calves grouped according to whether they were healthy (control group; G-1) or had diarrhea caused by K99 Escherichia coli (G-2; n = 10), bovine rota-or coronavirus (G-3; 5 each), or Cryptosporidium spp (G-4; 10). RESULTS Across the 3 time points at which blood samples were obtained and evaluated, the groups of calves with diarrhea generally had markedly higher mean serum concentrations of L-FABP, TFF-3, IAP, IL-8, and LP, compared with the control group. In addition, G-2 also consistently had markedly higher mean serum concentrations of I-FAB and ACTG2 and lower mean serum concentrations of CLDN-3, compared with the control group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that degree of intestinal epithelial damage differed among calves grouped by the etiologic agent of diarrhea and that such damage might have been more severe in calves with diarrhea caused by K99 E coli. Additionally, our results indicated that serum concentrations of I-FABP, L-FABP, TFF-3, IAP, IL-8, ACTG2, LP, and CLDN-3 were useful biomarkers of intestinal epithelial damage in calves of the present study., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [1160456], Funded by The Scientific and Technological Research Council of Turkey (TUBITAK; project No. 1160456).

WOS: 000494799400057, PubMed: 31230255, The study aimed to define the effects of M. haemolytica and a single oral dose of albendazole on the single-dose pharmacokinetics of marbofloxacin in lambs. The pharmacokinetic-pharmacodynamic integration of marbofloxacin was applied to describe a 3 mg/kg intramuscular dose in lambs. The 6 healthy and 12 naturally infected with M. haemolytica lambs (Akkaraman, males weighing 10-15 kg and aged 2-3 months) were used in this study. In the marbofloxacin group, 6 healthy lambs received marbofloxacin. In the albendazole group after 2 weeks washout period, the same animals received marbofloxacin on 1 h after albendazole. In the diseased marbofloxacin group, 6 lambs naturally infected with M. haemolytica received marbofloxacin. In the diseased albendazole group, 6 lambs naturally infected with M. haemolytica received marbofloxacin on 1 h after albendazole. The marbofloxacin and albendazole were administered each as a single dose of 3 mg/kg intramuscular and 7.5 mg/kg oral, respectively, in the respective groups. Plasma concentration of marbofloxacin was measured with HPLC-UV and pharmacokinetic parameters were analyzed by non-compartmental model. Albendazole did not change the pharmacokinetic profiles of marbofloxacin in healthy and diseased lambs. However, M. haemolytica affected the pharmacokinetics of marbofloxacin in diseased lambs, AUC(0-24)/MIC90 ratio was not found to be higher than 125, but C-max/MIC90 ratios was found to be higher than 10 for an MIC value of 0.25 mu g/mL in all groups. The marbofloxacin dose described in this study may not be effective for the treatment of infections due to M. haemolytica in lambs, with MIC

WOS: 000457396300021, PubMed: 30219998, This study investigated the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after single-dose intravenous (IV) administration (10mg/kg) of PTX in six healthy cattle. The safety of PTX was evaluated by clinical observation and biochemical analysis. Plasma concentrations of PTX and M-I were simultaneously determined by reverse-phase high performance liquid chromatography. Pharmacokinetic parameters were calculated using non-compartmental methods. Salivation and discomfort were observed for 2h following the drug administration. Serum direct bilirubin, total bilirubin, and phosphorus levels at 24h following the drug administration were significantly different from the control values (0h) (P

WOS: 000495358600031, The pharmaco-kinetic/dynamic of marbofloxacin was investigated after single intravenous (IV) and oral administration of 10 mg/kg in 192 healthy rainbow trout at 13 +/- 1.2 degrees C. The plasma concentrations of marbofloxacin were determined by high-performance liquid chromatography-ultraviolet detection. After IV and oral administration, the plasma concentration-time data were described by a noncompartmental analysis. The minimal inhibitory concentration (MIC) of marbofloxacin against Yersinia ruckeri, Aeromonas hydrophila, Pseudomonas fluorescens and P. putida were determined by broth dilution method at 13 degrees C. After IV administration, the elimination half-life (t(1/2)(lambda z)), area under the concentration-versus time curve (AUC(0-infinity)), apparent volume of distribution at steady-state and total body clearance of marbofloxacin were 18.05 h, 354.63 h * mu g/mL, 0.65 L/kg and 0.03 L/h/kg, respectively. After oral administration, t(1/2 lambda z), AUC(0)(-infinity) the peak plasma concentration, time of maximum concentration and bioavailability were 27.51 h, 135.29 h * mu g/mL, 3.74 mu g/mL, 4 h and 38.15%, respectively. The respective MICs of marbofloxacin against Y. ruckeri, A. hydrophila, P. fluorescens and P. putida were determined as 0.02 mu g/mL, 2.5 mu g/mL, 2.5 mu g/mL and 5 mu g/mL, respectively. Following IV and oral administration of 10 mg/kg marbofloxacin, AUC/MIC and C-max/MIC values were above the target levels for Y. ruckeri, while this dose was not sufficient for A. hydrophila and Pseudomonas spp. Because the pharmacokinetics and pharmacodynamics of a drug in fish are significantly affected by temperature, the dosage regimen of marbofloxacin should be modified according to temperature.

Çalışma, zosuquidar ve prazosin tarafından sırasıyla P-gp ve BCRP modülasyonunun AFB1'in plazma ve beyin konsantrasyonlarının etkileyip etkilemediğini belirlemek için gerçekleştirildi. Bu çalışmada, 40 adet sağlıklı, erkek BALB/c ırkı fare (323.7 g) kullanıldı. Hayvanlar her grupta 8 fare olacak şekilde rastgele 5 gruba ayrıldı. Grup 1, metod validasyon çalışmalarında kullanıldı. Grup 2 (AF)'ye AFB1 20 mg/kg dozda intraperitoneal yolla verildi. Grup 3 (AFPRZ), 4 (AFZQR) ve 5 (AFPRZZQR)'e ise sırasıyla intraperitoneal yolla prazosin (0.3 mg/kg), zosuquidar (25 mg/kg) ve prazosinzosuquidar (0.3 mg/kg prazosin 25 mg/kg zosuquidar) uygulamalarından 30 dk. sonra AFB1 20 mg/kg dozda intraperitoneal yolla uygulandı. Grup 2-5'de bulunan hayvanlardan AFB1 uygulamasından sonraki 6. saatte kan ve beyin örnekleri alındı. AFB1 düzeyleri fluoresans dedektör içeren HPLC sisteminde tayin edildi. Prazosin ve zosuquidarın tek ve eşzamanlı uygulanması AFB1'in beyin konsantrasyonlarında sadece AFB1uygulamasına göre önemli oranda azalmaya neden oldu (P0.05). AFB1 grubunda AFB1'in beyin/plazma oranı diğer gruplardan (AFPRZ, AFZQR, and AFPRZZQR) önemli oranda daha yüksekti (P0.05). Akut AFB1 zehirlenmelerinde özellikle BCRP gibi transmembran proteinlerin indüklenmesi hayatta kalma oranını artırabilir., This study was conducted to determine whether the plasma and brain concentrations of AFB1 are affected by the modulation of P-gp and BCRP using zosuquidar (ZQR) and prazosin (PRZ), respectively. In this study, a total of 40 healthy adult male BALB/c mice (32±3.7 g) were used. The animals were randomly divided into 5 groups, with 8 animals per group. Group 1 was used for method validation. Group 2 (AF) received intraperitoneal AFB1at a dose of 20 mg/kg of body weight. Groups 3 (AFPRZ), 4 (AFZQR), and 5 (AFPRZZQR) received 20 mg/kg of AFB1 intraperitoneally 30 min after the intraperitoneal administration of prazosin (0.3 mg/kg), zosuquidar (25 mg/kg), and prazosinzosuquidar (0.3 mg/kg prazosin 25 mg/kg zosuquidar), respectively. Six hours after the administration of AFB1, blood and brain samples were collected from the animals in Groups 2 to 5. AFB1concentrations were determined using an HPLC system with fluorescence detection. Individual and simultaneous administration of prazosin and zosuquidar significantly reduced the brain concentrations of AFB1 in comparison to a single administration of AFB1 (P