Pharmacokinetics of Marbofloxacin Following Oral Administration in Piperine, Quercetin Alone and Both in Combination Pretreated Broiler Chickens

Author(s):  
H.B. Patel ◽  
U.D. Patel ◽  
C.M. Modi ◽  
V.C. Ladumor ◽  
C.N. Makwana ◽  
...  

Background: Various antibacterial drugs are substrates for drug metabolizing enzymes. They suffer from reduced bioavailability after oral administration in chickens. Herbal bio-enhancers increased the absorption of co-administered drugs. Hence, present study was planned to explore the bio-enhancing effect of piperine and quercetin pretreatment on pharmacokinetics of marbofloxacin after oral administration in broiler chickens.Methods: The pharmacokinetics of marbofloxacin was investigated following single dose (5 mg/kg) oral administration in piperine, quercetin alone and both in combination pretreated (10 mg/kg each, oral, 3 days) broiler chickens. The concentrations of marbofloxacin in plasma samples were analyzed by high performance liquid chromatography.Result: Following single oral administration of marbofloxacin, elimination half-lives (t1/2β) were 6.23 ± 1.01, 5.69 ± 0.39 and 7.71 ± 0.59 h in piperine, quercetin and both in combination pretreated chickens, respectively. The elimination half-life (t1/2β), apparent volume of distribution (Vd(area)/F) and mean residence time (MRT) were significantly (p less than 0.05) higher in combination pretreated chickens as compared to piperine and quercetin alone groups. Piperine and quercetin combined pretreatment has improved the pharmacokinetics profile of marbofloxacin after oral administration in broiler chickens. Findings of the study are expedient for the development of protocol for use of bio-enhancers with antibiotics in broiler chickens.

2017 ◽  
Vol 5 (1) ◽  
pp. 57
Author(s):  
Mohamed Aboubakr ◽  
Mohamed Elbadawy

The pharmacokinetics (after single intravenous and oral dose) and tissue residues (orally and daily for five days) of cephradine (20 mg/kg b.wt.) were investigated in healthy and experimentally E.coli infected broiler chickens. Following single intravenous injection to healthy chickens, cephradine obeyed a two compartments open model and the elimination half-life (t1/2β), volume of distribution (Vdss) and total body clearance (CLtot) of cephradine were 2.93 h, 321.5 ml/kg and 0.08 L/h/kg, respectively. Following single oral administration of cephradine to healthy chickens, the peak serum concentration (Cmax) of it was 26.7 µg/mL and achieved (Tmax) at 2.41 h. The oral bioavailability of cephradine was 87.7%. Cephradine was assayed in kidney, liver, heart, gizzard, spleen, breast muscle, thigh muscle and skin after 24, 48, 72, 96 and 120 h after last dose. On conclusion, cephradine is a good choice for treatment of colisepticemia in chickens due to its higher oral bioavailability and distribution.


2004 ◽  
Vol 56 (6) ◽  
pp. 695-700
Author(s):  
E.J. Picco ◽  
D.C. Diaz David ◽  
T. Encinas ◽  
M.R. Rubio ◽  
J.C. Boggio

The pharmacokinetic profile of sodium meclofenamate, a non-steroidal antiinflammatory drug, was determined in six pre-ruminant calves after intravenous and intramuscular administration at a dose of 2.2mg/kg of body weight. Meclofenamate concentrations were measured using a high performance liquid chromatography assay. The pharmacokinetics of sodium meclofenamate after intravenous and intramuscular administration to calves were characterised by a rapid distribution phase (t½alpha ), 15.45± 4.85min and 23.14± 7.24min for the intravenous and intramuscular administration, respectively, followed by a longer elimination phase (t½beta ) after intramuscular treatment (17.55± 6.52h.). The apparent volume of distribution (Vd) of the drug after intravenous administration was moderate (0.72± 0.12l/kg), and high (3.51± 1.05l/kg) after intramuscular administration. This can be explained by the flip-flop effect or by enterohepatic shunting. The bioavailability achieved after intramuscular administration was 61%.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4769
Author(s):  
Sathish Nanjundappa ◽  
Suresh Narayanan Nair ◽  
Darsana Udayan ◽  
Sreelekha Kanapadinchareveetil ◽  
Mathew Jacob ◽  
...  

Amitraz, a member of the formamidine pesticide family, commonly used for ectoparasite control, is applied as a dip or low-pressure hand spray to cattle and swine, and the neck collar on dogs. Data on amitraz were generated mainly on laboratory animals, hens, dogs, and baboons. The data on the toxicity and disposition of amitraz in animals and its residues in the milk are inadequate. Therefore, the present study was intended to analyze the disposition kinetics of amitraz and its pattern of elimination in the milk of lactating does after a single dermal application at a concentration of 0.25%. Blood at predetermined time intervals and milk twice daily were collected for eight days post application. The drug concentration was assayed by high-performance liquid chromatography (HPLC). Amitraz was detected in whole blood as early as 0.5 h, which attained a peak concentration at 12 ± 5 h, followed by a steady decline; however, detection persisted until 168 h. Amitraz was present in the blood at its 50% Cmax even after 48 h, and was still detectable after 7 days. The disposition after a single dermal application was best described non-compartmentally. The mean terminal half-life (t1/2), mean residence time (MRT), and area under the curve (AUC0–t) were 111 ± 31 h, 168 ± 39 h, and 539 ± 211 µg/mL/h, respectively. The apparent volume of distribution (Vdarea) was 92 ± 36 mL/g with an observed clearance (Cl) of 0.57 ± 0.33 mL/kg/h. Thus, the drug was well absorbed, widely distributed and slowly eliminated from the animal body. Amitraz achieved milk concentration approximating 0.2 per cent of the total dose after a single exposure and the steady-state elimination of amitraz in milk above the recommended maximum residue limit (MRL) of 0.01 mg/kg can act as a source of public health concern when applied on lactating animals.


1986 ◽  
Vol 20 (9) ◽  
pp. 704-707 ◽  
Author(s):  
Maria J. Otero ◽  
Miguel Barrueco ◽  
Eduardo L. Marino ◽  
Francisco Gomez ◽  
Alfonso Dominguez-Gil

The influence of age on the disposition of theophylline was studied in 95 adult patients (nonsmokers) with bronchial asthma requiring oral theophylline therapy: 17 patients age ≥39 years, 50 patients age 40–59 years, and 28 patients < 60 years. A decrease was observed in total body clearance together with an increase in the elimination half-life of theophylline parallel to the advance in age of the patients. The apparent volume of distribution of theophylline was similar in the three groups of patients. According to the results obtained, recommendations are made regarding the dosage regimens of theophylline in elderly patients.


1988 ◽  
Vol 6 (8) ◽  
pp. 1321-1327 ◽  
Author(s):  
K A Rodvold ◽  
D A Rushing ◽  
D A Tewksbury

A study was carried out to examine the effect, if any, of obesity on doxorubicin pharmacokinetics. Body weight was found to be significantly related to doxorubicin clearance (r = -.75; P less than .001) and elimination half-life (r = .62; P = .003). Thus, the contribution of obesity on pharmacokinetics of antineoplastic agents should be taken into consideration in the analysis of clinical data with respect to toxicity and tumor response. Twenty-one patients were studied with their first course of doxorubicin (50 to 70 mg/m2) administered as a 60-minute intravenous (IV) infusion. Patients were divided into three groups on the basis of percentage of ideal body weight (IBW): normal (less than 115% IBW), mildly obese (115% to 130% IBW), and obese (greater than 130% IBW). Blood samples were collected up to 48 hours after the infusion and analyzed for doxorubicin and its metabolite, doxorubicinol, by high performance liquid chromatography. Doxorubicin area under the curve (AUC) was greater in obese than in normal patients (2,209 v 1,190 ng h/mL; P less than .05), yielding correspondingly reduced systemic clearance of the agent in obese patients (891 v 1,569 mL/min; P less than .001). The mean elimination half-life (T1/2) was 20.4 hours in the obese patients and 13.0 hours in the normal patients. The apparent volume of distribution (Vss) was not significantly different among the three groups of patients, indicating that the prolonged T1/2 in the obese patients is due to the reduction in clearance. The AUC and T1/2 of doxorubicinol were similar among all patient groups.


1987 ◽  
Author(s):  
L Bara ◽  
Y Le Roux ◽  
M Woler ◽  
F Chauliac ◽  
A Frydman ◽  
...  

The pharmacokinetics of enoxaparin (E) was randomly studied in 12 healthy male volunteers. Each dose (20-40-60 and 80 mg) was injected via subcutaneous (sc) route with a one-week wash out period. Anti-Xa and anti-IIa activities (ACT), calcium thrombin time (CTT) and Heptest were measured over a 36 hour period. E and the IV th International Heparin Standard were both used as internal standards.The anti IIa and CTT effects were only measurable when the injected dose was higher than 40 mg. The maximum anti-Xa and anti-IIa ACT were obtained 3 to 4 hours after the dose. As anti-IIa ACT is lower than anti-Xa ACT (anti-Xa/anti-IIa ACT ration I .6 to 2), the complete pharmacokinetic description of E was only based on anti-Xa data. Thus, the mean values of the maximal anti-Xa ACT (A max) were respectively: 1.58 ± 0.35 pg/ml; 3.83 ± 0.98 jig/ml, 5.38 ± 0.75 ug/ml and 7.44 ± 1.4 pg/ml for the four doses (20-40-60 and 80 mg). The resorption of E after sc injection was strictly linear whereas the relationships between A max or AUC in the one hand and dose in the other hand were A (anti Xa) Max = 0.0954 (dose) - 0,2083 r = 0.9146/p < 0.001; n = 48) and AUC (0 - 36 h) = 0.9117 (dose) - 7.59 (r = 0.9133/p < 0.001; n = 48). The mean residence time of E was close to 6 h (5.83 ± 0.86 h for D = 40 mg; 6.19 ± 0.74 h for D = 60 mg and 6.44 ± 0.76 h for 80 mg) indicating that around 50% of the total anti Xa ACT is induced in a 6 hour interval. The apparent volume of distribution V is close to 61 (6.59 1 ±1.33 1 for D = 60 mg) and the total Dody clearance is equal to 1.25 1/h, indicating the rate of depolymerisation of enoxaparin is lower than that of heparin. Plasma elimination half-life of anti-Xa ACT is equal to 4.36 ± 1.07 h (D = 40 mg) whereas that of anti-IIa ACT is shorter, fi) = 2.1 h). These results indicate that enoxaparin exhibits i) a differential anti-Xa/anti-IIa ACT profile, ii) a linear relationship between dose and anti-Xa/anti-IIa ACT and iii) a kinetic profile which is significantly different from that of standard heparin.


2003 ◽  
Vol 47 (4) ◽  
pp. 1395-1398 ◽  
Author(s):  
Chin-Chung Lin ◽  
Li-Tain Yeh ◽  
Trong Luu ◽  
David Lourenco ◽  
Johnson Y. N. Lau

ABSTRACT Absorption, pharmacokinetics, distribution, metabolism, and excretion of [14C]ribavirin were studied in rats (30 mg/kg of body weight) and cynomolgus monkeys (10 mg/kg) after intravenous (i.v.) and oral administration. The oral absorption and bioavailability were 83 and 59%, respectively, in rats and 87 and 55%, respectively, in monkeys. After i.v. administration, the elimination half-life (t [1/2]) was 9.9 h in rats and 130 h in monkeys and the total body clearance was 2,600 ml/h/kg in rats and 224 ml/h/kg in monkeys. The apparent volume of distribution was 11.4 liter/kg in rats and 29.4 liter/kg in monkeys. There was extensive distribution of drug-derived radioactivity into red blood cells and extensive metabolism of ribavirin in rats and a lesser degree of metabolism in monkeys. Excretion of total radioactivity in urine from rats accounted for 84% of the i.v. dose and 83% of the oral dose, whereas that from monkeys accounted for 47% of the i.v. dose and 67% of the oral dose. Several metabolites were observed in plasma and urine from both species. The amount of unchanged ribavirin in urine from both species was quite small after either i.v. or oral administration.


2021 ◽  
Author(s):  
Zhengrong Gao ◽  
Yu Liu ◽  
Yuxin Yang ◽  
Yuying Cao ◽  
Jicheng Qiu ◽  
...  

Abstract Background: Buserelin is a LHRH agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not clearly understood. This study was designed to develop a sensitive method to determine the concentration of buserelin and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results: A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studies in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h·ng/mL for pigs and 5.63 ±1.86 h·ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ±0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2λz), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion: This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.


Author(s):  
G.E. Swan ◽  
H.A. Koeleman ◽  
H.S. Steyn ◽  
M.S.G. Mülders

The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closantel and rafoxanide were characterised by a rapid distribution (t1/2(a) of <30 min), long elimination half-life (t1/2(b) of 17.0 + 4.0 days for closantel and 7.2 + 0.6 days for rafoxanide), small apparent volume of distribution (Vss of <0.15 ℓ/kg) and a slow rate of total body clearance (Cl of <0.01mℓ/min/kg). The area under the drug plasma concentration curve (AUC) of closantel at 5 mg/kg was nearly twice as large as that of rafoxanide at 7.5 mg/kg resulting from the slower t1/2(b) observed with closantel compared to rafoxanide. Large individual differences were observed in the rate measurements of distribution (k12, k21 and t1/2(a)), whereas the parameters of elimination (k10, t1/2(b) and Cl), were more consistent between animals. A dose proportional increase in AUC was observed for closantel administered at 5 and 15 mg/kg. A low, constant salivary concentration of closantel (mean of 0.04+0.05 mg/mℓ) and rafoxanide (mean of 0.07+0.04 mg/mℓ) was observed during the 24-h examination period after dosing.


Author(s):  
Mohamed Aboubakr ◽  
Mohamed Elbadawy

Background: Pharmacokinetic study of a commercial tylosin-doxycycline combination product (D-Tylo50/25®) was conducted in broiler chickens following intravenous (IV) and oral (PO) administration at doses of 50 mg/kgb. wt. (tylosin) and 25 mg/kg b. wt. (doxycycline).Methods: Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection.Results: A rapid and nearly complete absorption of both drugs with a mean PO bioavailability of 89.16% (tylosin) and 94.30% (doxycycline), prolonged elimination half-lives, and high tissue penetration with steady state volume of distribution of 6.73L/kg (tylosin) and 5.51L/kg (doxycycline) were observed. Tissue residues were studied following oral administration of each drug alone for fiveconsecutive days and blood and tissue samples were obtained for 10 days after the last dose. Residues of tylosin and doxycyclines showed that kidney, liver and lung contained highest drug residues and completely disappeared from those tissues at 5 and 6 days after the last oral dose, respectively. The efficacies of D-Tylo50/25® and other antibiotics (tiamulin and oxytetracyline) were investigated in broiler chicks experimentally infected by Mycoplasma gallisepticum.Conclusions: The pharmacokinetics of both drugs was characterized by a rapid and complete absorption, extensive tissue distribution and slow elimination. D-Tylo50/25® is more effective than tiamulin and oxytetracycline against Mycoplasma gallisepticum infection in broilers.


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