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.

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 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 Pharmacokinetics of sodium meclofenamate in pre-ruminant cattle

2004 ◽  
Vol 56 (6) ◽  
pp. 695-700
Author(s):  
E.J. Picco ◽  
D.C. Diaz David ◽  
T. Encinas ◽  
M.R. Rubio ◽  
J.C. Boggio
Keyword(s):  
High Performance ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Antiinflammatory Drug ◽  
Volume Of Distribution ◽  
Intramuscular Administration ◽  
Flip Flop ◽  
Elimination Phase ◽  
Distribution Phase ◽  
Apparent Volume Of Distribution

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%.

Doxorubicin clearance in the obese.

1988 ◽  
Vol 6 (8) ◽  
pp. 1321-1327 ◽  
Author(s):  
K A Rodvold ◽  
D A Rushing ◽  
D A Tewksbury
Keyword(s):  
Body Weight ◽  
Half Life ◽  
High Performance ◽  
Area Under The Curve ◽  
Ideal Body Weight ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Obese Patients ◽  
Elimination Half Life ◽  
Elimination Half

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.

An HPLC–MS/MS method for quantitation of trelagliptin and application in a comparative pharmacokinetic study

Bioanalysis ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 1755-1765
Author(s):  
Ying Han ◽  
Liqing Chen ◽  
Wei Liu ◽  
Xin Xin ◽  
Lingwei Meng ◽  
...  
Keyword(s):  
Ion Pairs ◽  
Area Under The Curve ◽  
Internal Standard ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Distribution Area ◽  
Comparative Pharmacokinetic ◽  
Positive Mode ◽  
First Time ◽  
Apparent Volume Of Distribution

Aim: A sensitive HPLC–MS/MS approach was established to quantify trelagliptin and explore the pharmacokinetic characteristics in rats for up to 7 days. Meanwhile, the pharmacokinetic differences of trelagliptin were investigated for the first time. Results/methodology: The ion pairs of m/z 358.2→341.2 for trelagliptin and m/z 340.3→116.1 for alogliptin (internal standard) were detected in positive mode. Trelagliptin displayed a good linearity in the range of 4–4000 ng/ml (r2 = 0.9997) with a mean recovery rate of 86.9–94.1%. Discussion/conclusion: Compared with normal groups, the T1/2, apparent volume of distribution, area under the curve and bioavailability in model rats were significantly increased while the apparent plasma clearance decreased. The approach is proved to be straightforward and appropriate for quantitation of trelagliptin and application in pharmacokinetics studies.

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

2021 ◽  
Author(s):  
H.B. Patel ◽  
U.D. Patel ◽  
C.M. Modi ◽  
V.C. Ladumor ◽  
C.N. Makwana ◽  
...  
Keyword(s):  
Oral Administration ◽  
Broiler Chickens ◽  
High Performance ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolizing Enzymes ◽  
Single Oral Administration ◽  
Elimination Half ◽  
Combined Pretreatment ◽  
Apparent Volume Of Distribution

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.

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.

Model of the distribution and metabolism of a GnRH superagonist in dogs

1990 ◽  
Vol 258 (3) ◽  
pp. E468-E475
Author(s):  
D. Lacoste ◽  
B. Candas ◽  
M. Normand ◽  
F. Labrie
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Gonadotropin Releasing Hormone ◽  
Metabolic Clearance ◽  
Sigmoid Function ◽  
Subcutaneous Route ◽  
Metabolic Clearance Rate ◽  
Fractional Rate ◽  
Kinetics Of ◽  
Apparent Volume Of Distribution

The plasma kinetics of [D-Trp6, des-Gly-NH2(10)]gonadotropin-releasing hormone (GnRH) ethylamide was assessed in eight dogs over a period of 8 h after rapid intravenous or subcutaneous injection. Each animal received doses of 0.2, 2, and 20 micrograms/kg body wt iv and 1 and 10 micrograms/kg body wt sc. A two-compartment structure, to which a source compartment was added to represent the subcutaneous route, adequately fits the five kinetics when the apparent volume of distribution follows a plasma concentration-dependent sigmoid function. Despite the nonlinearity, the apparent volume of distribution can be approximated by a constant value of 280 ml/kg body wt for the dynamics corresponding to the three lowest and more physiological doses. The metabolic clearance rate is 4.63 ml.min-1.kg body wt-1. The two exponential components that characterize the two-compartment structure are equal to 0.0348 +/- 0.0053 and 0.00470 +/- 0.00060 min-1, respectively. The agonist injected subcutaneously diffuses to plasma at a fractional rate of 0.0265 +/- 0.0029 min-1. Disposal occurs at a maximal rate of 0.017 and 0.0055 min-1 of the amount of agonist present in the central and peripheral compartments, respectively. The highest fractional exchange rate between compartments reaches 0.01 min-1. As simulated with the model, a continuous infusion of 4.63 ng.min-1.kg body wt-1 leads to a steady state of 1 ng/ml plasma; 90% of that level is reached 7 h after the onset of the subcutaneous input signal. The kinetics of plasma [D-Trp6, des-Gly-NH2(10)]GnRH ethylamide is many times slower than that of the native hormone and of the other GnRH agonists.

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.

scholarly journals Disposition Kinetics of Levofloxacin in Sheep after Intravenous and Intramuscular Administration

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Ayman Goudah ◽  
Sherifa Hasabelnaby
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Volume Of Distribution ◽  
Intramuscular Administration ◽  
Uv Detector ◽  
Disposition Kinetics ◽  
Systemic Bioavailability ◽  
Kinetics Of

The present study was planned to investigate the disposition kinetics of levofloxacin in plasma of female native Barky breed sheep after single intravenous (IV) and intramuscular (IM) administration of 4 mg/kg body weight. The concentrations of levofloxacin in the plasma were measured using high-performance liquid chromatography (HPLC) with a UV detector on samples collected at 0, 0.08, 0.16, 0.33, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 32, and 48 h after treatment. Following intravenous injection, the decline in plasma drug concentration was biexponential with half-lives of  h and  h for distribution and elimination phases, respectively. The volume of distribution at steady state was  l/kg. After intramuscular administration of levofloxacin at the same dose, the peak plasma concentration was  g/mL and was obtained at  h , the elimination half-life was  h, and AUC was  g.h/mL. The systemic bioavailability was %.In vitroplasma protein binding was 23.74%. When approved therapy fails, levofloxacin may be used in some countries for therapy of food animals, however, that is not true in the US.

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