The Pharmacokinetics of Buserelin after Intramuscular Administration in Pigs and Cows

2021 ◽  
Author(s):  
Zhengrong Gao ◽  
Yu Liu ◽  
Yuxin Yang ◽  
Yuying Cao ◽  
Jicheng Qiu ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Apparent Volume ◽  
Ultra Performance Liquid Chromatography ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Elimination Half ◽  
Liquid Chromatography Tandem Mass ◽  
Stability Method ◽  
Apparent Volume Of Distribution

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.

scholarly journals Influence of Resveratrol on the Pharmacokinetics and Pharmacodynamics of Naproxen: Involvement of CYP1A2 Inhibition

2018 ◽  
Vol 1 (1) ◽  
pp. 01-03
Author(s):  
Prasad Neerati
Keyword(s):  
Single Dose ◽  
Area Under The Curve ◽  
Treatment Phase ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Maximum Plasma ◽  
Time Intervals ◽  
Novel Approach ◽  
Gastrointestinal Side Effects ◽  
Apparent Volume Of Distribution

The purpose of the present study was to assess the effect of resveratrol (RSV) on the pharmacokinetics of naproxen (NAP) in rats. A single dose of RSV 30mg/kg was administered once during treatment phase. A single dose of NAP 25mg/kg was administered after RSV treatment. The blood samples were collected after NAP dosing at predetermined time intervals and analyzed by HPLC. In comparison with the control, RSV pretreatment significantly enhanced maximum plasma concentration (Cmax), area under the curve (AUC), and half life (t1/2) and significantly decreased apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F), while there was no significant change observed in time to reach maximum concentration (tmax) of NAP. The results suggest that the altered pharmacokinetics of NAP might be attributed to RSV-mediated inhibition of CYP1A2 enzyme. Therefore, combination therapy of NAP along with RSV may represent a novel approach to reduce dosage and results in reduced gastrointestinal side effects of NAP.

Ketamine kinetics: decerebrate vs. intact cats

1979 ◽  
Vol 57 (8) ◽  
pp. 878-881 ◽  
Author(s):  
James E. Heavner ◽  
Duane C. Bloedow
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Peripheral Compartment ◽  
Blood Concentrations ◽  
Open Model ◽  
Apparent Volume Of Distribution ◽  
Compartment Open Model

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p < 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.

Letters to the Editor

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 602-603
Author(s):  
Charles H. Feldman ◽  
Vincent E. Hutchinson ◽  
Charles E. Pippenger ◽  
Thomas A. Blumenfeld ◽  
Bernard R. Feldman ◽  
...  
Keyword(s):  
Elimination Rate ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Apparent Volume ◽  
Systemic Circulation ◽  
Volume Of Distribution ◽  
Letters To The Editor ◽  
Correct Formula ◽  
Original Report ◽  
Apparent Volume Of Distribution

We appreciate the comments of Weinberger et al and Spino et al. The equation utilized in our original report to calculate the apparent volume of distribution (V) was in error, as it was based on determinations for drugs that exhibit monoexponential elimination following a single intravenous dose. The correct formula for oral dosing at steady state with a drug obeying one-compartment model kinetics is: V = F.X0/AUCτ. K, where F is the total fraction of dose reaching systemic circulation, X0, is the dose, AUCτ is the area under the curve during a dosing interval; K is the elimination rate constant.1

scholarly journals Effects of Xuesaitong on the Pharmacokinetics of Losartan: An In Vivo UPLC-MS/MS Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Weina Ma ◽  
Lei Lv ◽  
Jungang Guo ◽  
Yongjun Meng ◽  
Yinghua Wang ◽  
...  
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Blood ◽  
Apparent Volume Of Distribution ◽  
Noncompartmental Model

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

scholarly journals PHARMACOKINETIC STUDIES OF A CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEM OF LORNOXICAM BY LC-MS/MS METHOD

2018 ◽  
Vol 10 (6) ◽  
pp. 88
Author(s):  
Sindhu Abraham ◽  
Rajamanickam Deveswaran ◽  
Jayaraman Anbu ◽  
Sharon Furtado ◽  
Bharath Srinivasan
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Maximum Concentration ◽  
Area Under The Curve ◽  
Immediate Release ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Half ◽  
Coated Tablet ◽  
Liquid Chromatography Tandem Mass

Objective: The objective of this study was to investigate differences in pharmacokinetic patterns of immediate release tablet (IR) and compression coated tablet (CCT) of lornoxicam, proposed for the chronotherapeutic treatment of rheumatoid arthritis.Methods: The dosage forms were administered to two groups of white New Zealand rabbits (n=3), and the plasma drug levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters like maximum concentration (Cmax), time is taken to reach maximum concentration (Tmax), area under the curve (AUC), elimination half-life (t1/2) and Mean Residence Time (MRT) were determined.Results: In the case of IR tablets, the drug was detected within 15 min after oral administration and a Cmax of 1269.57±4.04 ng/ml were attained at 2±0.15 h. With CCT, the drug was detected only after 5 h and a Cmax of 1279.24±12.76 ng/ml were attained at 8±0.10 h. The CCT showed maximum drug release at the eighth hour in comparison to IR tablet which showed maximum release at the second hour of study.Conclusion: The predominant lag time prior to drug release from CCT is an indication that it is consistent with the requirements of chronopharmaceutical drug delivery. The results suggest that the compression coated tablet is a promising approach for chronotherapeutic management of rheumatoid arthritis.

scholarly journals Busulfan disposition in children

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1723-1727 ◽  
Author(s):  
LB Grochow ◽  
W Krivit ◽  
CB Whitley ◽  
B Blazar
Keyword(s):  
Drug Disposition ◽  
Area Under The Curve ◽  
Lysosomal Storage Diseases ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Severe Toxicity ◽  
Lysosomal Storage ◽  
Elimination Half ◽  
Actual Volume ◽  
Low Incidence

Children receive busulfan orally as part of myeloablative therapy before bone marrow transplantation for malignant and nonmalignant conditions. Children have been reported to have a low incidence of severe toxicity and significant rates of failure to achieve full engraftment. We evaluated the disposition of busulfan in children between 2 months and 3.6 years of age with lysosomal storage diseases, leukemia, and immunodeficiency disorders receiving oral doses of 1 or 2 mg/kg using a gas chromatographic assay. Peak concentrations were lower than those previously reported for adults, ranging from 1.4 to 5.2 mumol/L. The harmonic mean of the elimination half-life was 92 minutes, which is only slightly faster than that for adults (140 minutes). However, the area under the curve ranged from 400 to 1,000 (715 +/- 240) mumol.min/L, substantially lower than in adults receiving 1 mg/kg (range, 710 to 5,100 mumol.min/L; mean +/- SD, 2,180 +/- 1,200). The apparent volume of distribution (assuming complete bioavailability) ranged from 0.28 to 3.53 L/kg (1.42 +/- 0.86), which is more than twice that reported for adults (0.60 +/- 0.42). Busulfan clearance rate normalized to surface area is twice as high in children (200 +/- 100 mL/min/m2) as it is in adults (95 +/- 54 mL/min/m2). Alterations in bioavailability (absorption or first pass elimination) or in actual volume of distribution may account for these differences in drug disposition. The observed differences suggest the need for separate phase I dose escalation studies in children with accompanying pharmacokinetic assessment.

scholarly journals Disposition Kinetics of Amitraz in Lactating Does

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4769
Author(s):  
Sathish Nanjundappa ◽  
Suresh Narayanan Nair ◽  
Darsana Udayan ◽  
Sreelekha Kanapadinchareveetil ◽  
Mathew Jacob ◽  
...  
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Health Concern ◽  
Laboratory Animals ◽  
Disposition Kinetics ◽  
Kinetics Of ◽  
Apparent Volume Of Distribution ◽  
Dermal Application

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.

scholarly journals Plasma pharmacokinetics of ciprofloxacin in sheep

1970 ◽  
Vol 6 (1) ◽  
pp. 93-97
Author(s):  
MS Islam ◽  
MMH Sikder ◽  
MA Awal ◽  
M Mostofa ◽  
AA Trisha
Keyword(s):  
Half Life ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sheep Model ◽  
First Order Kinetics ◽  
Healthy Sheep ◽  
Plasma Pharmacokinetics ◽  
Total Body

The study was carried out to determine the biodisposition kinetics of ciprofloxacin in sheep model in Department of Pharmacology, Bangladesh Agricultural University. Healthy sheep of both sexes (n=65) were divided into 13 groups, each consists of five and given a single dose of ciprofloxacin @ 5 mg/kg bwt intramuscularly .Blood sample was collected from each group of sheep at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10 and 12 hours interval respectively. Serum concentration of ciprofloxacin was determined by spectrophotometric method. The pharmacokinetic parameters were measured by single compartment open model and first order kinetics. The peak concentration of ciprofloxacin was 3.56±0.15mg/ ml, absorption half-life and biological half-life were 0.0846±1.79 and 1.75±0.15 h respectively. The apparent volume of distribution was found 35.54 mg/liter. The absorption rate constant was 8.188h-1, MRT was 2.647h-1 and total body clearances were found 16.88 h-1. These result suggested that a dose of 5 mg/kg bwt provides maximum plasma concentration and is effective in the control of many infectious diseases of sheep. Key words: Plasma pharmacokinetics, ciprofloxacin, sheep DOI = 10.3329/bjvm.v6i1.1344 Bangl. J. Vet. Med. (2008). 6 (1): 93-97

scholarly journals Pharmacokinetic Study of Modafinil in Relation to Gender and Ethnicity in Healthy Young Chinese Volunteers

2010 ◽  
Vol 13 (3) ◽  
pp. 443 ◽  
Author(s):  
Tao Guo ◽  
Longshan Zhao ◽  
Dong-Ya Xia
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
High Performance ◽  
Area Under The Curve ◽  
Total Body Weight ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Significant Difference ◽  
Total Body

Purpose. The pharmacokinetics of modafinil were investigated in relation to gender and ethnicity in healthy young volunteers from Han, Mongolian, Korean, Uygur and Hui ( n = 10/group) following administration of a single 200 mg oral dose. Methods. Blood samples were collected over 48 h for the determination of plasma levels of modafinil and its acid metabolite by High performance liquid chromatography with an ultraviolet detector. Pharmacokinetic parameters were evaluated using noncompartmental methods. Results. Modafinil was well tolerated and safe at a single oral dose of 200 mg. All participants reported adverse events, none of which was serious or unexpected. The maximum plasma concentration (Cmax) and area under the curve for modafinil concentration versus time, which was extrapolated to infinity (AUC0-∞), were higher in women compared to men (p < 0.01). No gender-based difference was noted in the total body weight-normalized modafinil oral clearance. The total body weight-normalized modafinil apparent volume of distribution and the t1/2 was found to exhibit an ethnicity-based significant difference. Conclusion. The results of the current study suggest that there might be pharmacokinetic differences related to gender and ethnicity in the pharmacokinetics of modafinil.

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