scholarly journals Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin in Pig against Korean Local Isolates ofActinobacillus pleuropneumoniae

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Md. Akil Hossain ◽  
Hae-chul Park ◽  
Kyunghun Jeong ◽  
Yang ho Jang ◽  
Dae Gyun Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Antibacterial Activities ◽  
Time Intervals ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean

The pharmacokinetics of marbofloxacin in pigs after intravenous (i.v.), intramuscular (i.m.), and peroral (p.o.) administration and pharmacokinetic/pharmacodynamic indices of this drug against Korean local isolates ofActinobacillus pleuropneumoniaewere determined in this study. Marbofloxacin (2.50 mg/kg of body weight) was administered, and blood samples were collected with designated time intervals. Plasma-extracted marbofloxacin was injected into the LC-MS/MS system. The in vitro and ex vivo antibacterial activities of marbofloxacin were evaluated against 20 isolates ofA. pleuropneumoniae. The mean peak plasma concentrations (Cmax) after i.v., i.m., and p.o administration were2.60±0.10,2.59±0.12, and2.34±0.12 µg/mL at0.25±0.00,0.44±0.10, and1.58±0.40 h, respectively. The area under the plasma concentration-time curves (AUC0–24) and elimination half-lives were24.80±0.90,25.80±1.40, and23.40±5.00 h·μg/mL and8.60±0.30,12.80±1.10, and8.60±0.00 h, for i.v., i.m., and p.o. administration, correspondingly. The AUC0–24/MICs of marbofloxacin after i.v., i.m., and p.o. administration were253.86±179.91,264.1±187.16, and239.53±169.75 h, respectively. TheCmax/MIC values were26.58±18.84,26.48±18.77, and23.94±16.97, and T>MICs were42.80±1.01,36.40±1.24, and38.60±1.18 h, after i.v., i.m., and p.o. administration, respectively. Thus, marbofloxacin dosage of 2.50 mg/kg of body weight by i.v., i.m., and p.o. administration with 24 h dosing interval will provide effective treatment for the infection of pig byA. pleuropneumonia.

Inhibitory Effect of Piracetam on Platelet-rich Thrombus Formation in an Animal Model

1998 ◽  
Vol 79 (01) ◽  
pp. 222-227 ◽  
Author(s):  
F. Stockmans ◽  
W. Deberdt ◽  
Å. Nyström ◽  
E. Nyström ◽  
J. M. Stassen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Thrombus Formation ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Cell Deformability

SummaryIntravenous administration of piracetam to hamsters reduced the formation of a platelet-rich venous thrombus induced by a standardised crush injury, in a dose-dependent fashion with an IC50 of 68 ± 8 mg/kg. 200 mg/kg piracetam also significantly reduced in vivo thrombus formation in rats. However, in vitro aggregation of rat platelets was only inhibited with piracetam-concentrations at least 10-fold higher than plasma concentrations (6.2 ± 1.1 mM) obtained in the treated animals. No effects were seen on clotting tests.In vitro human platelet aggregation, induced by a variety of agonists, was inhibited by piracetam, with IC50’s of 25-60 mM. The broad inhibition spectrum could be explained by the capacity of piracetam to prevent fibrinogen binding to activated human platelets. Ex vivo aggregations and bleeding times were only minimally affected after administration of 400 mg/kg piracetam i.v. to healthy male volunteers, resulting in peak plasma levels of 5.8 ± 0.3 mM.A possible antiplatelet effect of piracetam could be due to the documented beneficial effect on red blood cell deformability leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations were needed to prevent stirring-induced “spontaneous” platelet aggregation in human whole blood.It is concluded that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall itself must therefore be taken into consideration.

EFFECT OF THE CALCIUM CHANNEL BLOCKER, NIFEDIPINE, ON HAEMOSTASIS, CLOTTING, AND THROMBOLYSIS EX VIVO.

1987 ◽  
Author(s):  
M Rademaker ◽  
R H Meyrick Thomas ◽  
J D Kirby ◽  
I B Kovaos
Keyword(s):  
Oral Dose ◽  
Calcium Channel ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Channel Blockers ◽  
Clotting Time ◽  
Polyethylene Tubing

Nifedipine, as other calcium channel blockers, has been shown to inhibit platelet aggregation induced by various agonists in vitro. The therapeutic relevance of these findings are, however, questionable, as in vitro inhibition of platelet function occurs at plasma concentrations of nifedipine in excess of 50 uM, while the peak plasma concentration following a single 10 mg oral dose of nifedipine is only 0.2 uM. We have used the Haemostatometer, to assess the effect of nifedipine on haemostasis ex vivo. This instrument allows quantitative assessment of haemostasis by monitoring the pattern of haemostatic plug formation (HPF) in holes punched through polyethylene tubing through which non-anticoagulated blood flows under standard conditions (1,2). The pattern and speed of blood coagulation subsequent to HPF was measured as was the spontaneous thrombolysis time (STT) (taken as the time until expulsion of the haemostatic plug from heparinised blood). All values are for mean + SEM.Blood samples were taken from 10 healthy volunteers before and ninety minutes after a single 10 mg oral dose of nifedipine. Following nifedipine, the initial phase of the haemostatic reaction (HPF) was prolonged from 0.95 ± 0.12 min to 1.57 ± 0.14 min, (p< 0.01); clotting time was also increased from 13.1 ± 1.1 min to 20.7 ± 2.3 min, (p=0.013), and the STT fell from 48.0 ± 9.9 min to 27.5 ± 4.6 min (p=0.014).The increased bleeding time (HPF) provides evidence that a therapeutic dose of nifedipine evokes an anti-platelet effect. The prolongation of the clotting time seen in this study could be explained by,an effect of nifedipine on platelets and hence clotting. The mechanism of the enhanced spontaneous thrombolysis following nifedipine is not known.We suggest that the effect of nifedipine on haemostasis and thrombolysis may contribute to its therapeutic effect.(1) Gorog P and Kovacs I B. Haemostasis 16: 337-345, 1986.(2) Gorog P. Angiology 37: 99-105, 1986.

scholarly journals Bioavailability and pharmacokinetics of cefotaxime in Muscovy ducks

2016 ◽  
Vol 4 (1) ◽  
pp. 93 ◽  
Author(s):  
Mohamed Aboubakr
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Maximum Plasma ◽  
Mean Values ◽  
Elimination Half ◽  
Maximal Plasma ◽  
The Mean ◽  
Muscovy Ducks

The pharmacokinetic profile of cefotaxime following a single intravenous (IV) and intramuscular (IM) injection was studied in Muscovy ducks. Cefotaxime was given at a dose rate of 25 mg/kg b.wt. for both routes. After IV injection, the plasma levels of cefotaxime estimated at 0.08 h was 70.87 μg/ml, which declined gradually and cefotaxime was detected up to 10 h (0.59 μg/ml). The mean values of CL, Vdss and t1/2β of cefotaxime in muscovy ducks were 0.22 l/kg/h, 0.51 l/kg and 1.81 h, respectively. After IM injection, maximum plasma concentration (Cmax) was (14.72 μg/ml), time of maximal plasma concentration (tmax) was (2.3 h) and elimination half-life (t1/2el)was (1.77 h). Bioavailability following IM injection was 79.61%, and in vitro protein binding percent was 31.48%. A recommended IM dosage for cefotaxime in muscovy ducks would be 30 mg/kg b.wt., repeated at 12 h intervals will provide a therapeutic plasma concentrations exceeding the MIC≤0.5 µg/ml for most susceptible pathogens in ducks.

Oral Pharmacokinetics of Fluazifop-Butyl in Human Volunteers

1991 ◽  
Vol 10 (1) ◽  
pp. 39-43 ◽  
Author(s):  
B.H. Woollen ◽  
T.B. Hart ◽  
P.L. Batten ◽  
W.J.D. Laird ◽  
D.S. Davies ◽  
...  
Keyword(s):  
Body Weight ◽  
Active Ingredient ◽  
Half Life ◽  
Pharmacokinetic Model ◽  
Serum Proteins ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Elimination Half ◽  
Human Volunteers ◽  
Oral Pharmacokinetics

1 Fluazifop-butyl, the active ingredient of FUSILADE, a selective herbicide, was administered orally to three male volunteers at a dose level of 0.07 mg kg-1 body weight. Over a period of 6 d between 80 and 93% of the dose was excreted in urine as the metabolite fluazifop, the majority within the first 24 h. Peak plasma concentrations of fluazifop occurred 1-2.5 h after administration. 2 The elimination of fluazifop from plasma and urine can be described by a one-compartment pharmacokinetic model and the elimination half-life was estimated from blood and urine data to be within the range 9-37 h. Fluazifop was found to bind to serum proteins. 3 The study indicates that the amount of fluazifop-butyl absorbed in exposed persons can be assessed by measuring fluazifop concentrations in urine.

Azithromycin: An Assessment of Its Pharmacokinetics and Therapeutic Potential in CAPD

2001 ◽  
Vol 21 (4) ◽  
pp. 372-377 ◽  
Author(s):  
James R. Kent ◽  
Michael K. Almond ◽  
Soraya Dhillon
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Therapeutic Potential ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Future Research ◽  
Renal Unit ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean

Background Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity. Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin. This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Objective This study aimed to define the potential role of azithromycin in treating CAPD peritonitis. Design The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin. Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography. Setting The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom. Patients Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day). Results Peak plasma concentrations occurred at 2 -3 hours with 0.35 - 1.35 mg/mL (mean 0.75). The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8 hours, the mean dialysate concentration was 0.07 mg/mL; PD clearance was 0.06 L/hr. Conclusion Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present. However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported. Future research should address this possibility.

scholarly journals Pharmacokinetics and Inflammatory Fluid Penetration of Intravenous Daptomycin in Volunteers

2002 ◽  
Vol 46 (1) ◽  
pp. 31-33 ◽  
Author(s):  
R. Wise ◽  
T. Gee ◽  
J. M. Andrews ◽  
B. Dvorchik ◽  
G. Marshall
Keyword(s):  
Body Weight ◽  
Standard Deviation ◽  
Total Drug ◽  
Healthy Male ◽  
Urinary Recovery ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Fluid Penetration

ABSTRACT The lipopeptide antimicrobial daptomycin was administered intravenously at a dose of 4 mg/kg of body weight to seven healthy male volunteers. The concentrations of daptomycin in plasma, cantharidin-induced inflammatory fluid, and urine were measured by a microbiological assay. The mean ± standard deviation peak concentrations in plasma and inflammatory fluid were 77.5 ± 8.3 and 27.6 ± 9.5 μg/ml, respectively; the mean terminal elimination half-lives were 7.74 and 13.2 h, respectively. The overall penetration of total drug into the inflammatory fluid (measured by ratio of the area under the concentration-time curve from 0 to 24 h for inflammatory fluid compared with that for plasma) was 68.4%. The mean urinary recovery over 24 h was 59.7%.

scholarly journals 9-cis retinoic acid induces complete remission but does not reverse clinically acquired retinoid resistance in acute promyelocytic leukemia

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3021-3027 ◽  
Author(s):  
WH Jr Miller ◽  
A Jakubowski ◽  
WP Tong ◽  
VA Miller ◽  
JR Rigas ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pharmacokinetic Studies ◽  
Nb4 Cells ◽  
Drug Concentrations ◽  
Clinical Resistance ◽  
The Mean

9-cis retinoic acid (RA) is a high-affinity ligand for both retinoic acid receptors (RARs) and retinoid “X” receptors (RXRs). Although all-trans RA does not bind to RXRs, RAR/RXR heterodimers or RXR/RXR homodimers bind to specific DNA response elements and modulate proliferation and differentiation of normal and malignant cells. Because the development of clinical resistance to all-trans RA has been associated with a progressive decrease in plasma drug concentrations, we evaluated the ability of 9-cis RA to induce in vitro cytodifferentiation in subclones of a retinoid-sensitive and resistant APL cell line (NB4) and in short-term cultures of fresh leukemic cells aspirated from patients. We also evaluated the clinical activity and pharmacokinetics of 9-cis RA (LGD 1057) in patients with APL who were previously treated with all-trans RA. In vitro tests of both retinoid-sensitive NB4 cells, as well as samples of fresh cells from 11 patients with APL, showed relatively equivalent degrees of sensitivity to both 9-cis RA and all-trans RA at concentrations ranging from 10(-6) to 10(-8) mol/L; however, no substantial cytodifferentiation was observed using either drug alone or in combination (10(-6) mol/L of each) in retinoid-resistant NB4 cells. Seven patients with APL who had previously relapsed from a remission induced by all-trans RA were treated with 9-cis RA at daily oral doses ranging from 30 to 230 mg/m2. Pharmacokinetic studies showed that the mean terminal plasma half-life of 9-cis RA (1.3 hours) changed very little after several weeks of dosing, although the mean change per dose level in area under the plasma concentration x time curves and peak plasma concentrations showed a decrease by 49% and 45%, respectively. Peak plasma concentrations equaled or exceeded concentrations that were effective against retinoid-sensitive cells in vitro. Despite these favorable pharmacokinetic results, only one of the seven patients achieved complete remission, corroborating in vitro studies of blasts from three of the nonresponders that showed a relatively equivalent degree of resistance to both retinoids. Our results suggest that while 9-cis RA may not induce its own catabolism to the same degree as all-trans RA, this feature does not appear to overcome clinically acquired resistance to all-trans RA in APL. Nonetheless, the drug can induce complete remissions in patients with APL and may be useful for extended therapy in other diseases. Future studies should address the use of lower doses in patients who have not previously received retinoid therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro

2021 ◽  
Vol 22 (6) ◽  
pp. 3163
Author(s):  
Hirofumi Ohashi ◽  
Feng Wang ◽  
Frank Stappenbeck ◽  
Kana Tsuchimoto ◽  
Chisa Kobayashi ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Cultured Cells ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Membrane Vesicles ◽  
Drug Candidates ◽  
Increased Risk ◽  
Derivatives Of

The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.

scholarly journals Influence ofABCC2andABCC4Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients

2015 ◽  
Vol 59 (6) ◽  
pp. 3240-3245 ◽  
Author(s):  
Kanokrat Rungtivasuwan ◽  
Anchalee Avihingsanon ◽  
Narukjaporn Thammajaruk ◽  
Siwaporn Mitruk ◽  
David M. Burger ◽  
...  
Keyword(s):  
Body Weight ◽  
Multivariate Analysis ◽  
Plasma Concentration ◽  
Protease Inhibitors ◽  
Demographic Data ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
The Mean

ABSTRACTTenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded byABCC2andABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms ofABCC2andABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and theABCC44131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having theABCC44131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.)

scholarly journals Toxicity and Pharmacokinetic Studies of Lidocaine and Its Active Metabolite, Monoethylglycinexylidide, in Goat Kids

Animals ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 142
Author(s):  
Dinakaran Venkatachalam ◽  
Paul Chambers ◽  
Kavitha Kongara ◽  
Preet Singh
Keyword(s):  
Total Dose ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Lidocaine Hydrochloride ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Liquid Chromatography Mass Spectrometry ◽  
Elimination Half ◽  
The Mean ◽  
Safe Dose

This study determined the convulsant plasma concentrations and pharmacokinetic parameters following cornual nerve block and compared the results to recommend a safe dose of lidocaine hydrochloride for goat kids. The plasma concentrations of lidocaine and monoethylglycinexylidide (MGX) were quantified using liquid chromatography-mass spectrometry. A total dose of 7 mg/kg body weight (BW) was tolerated and should therefore be safe for local and regional anesthesia in goat kids. The mean plasma concentration and mean total dose that produced convulsions in goat kids were 13.59 ± 2.34 µg/mL and 12.31 ± 1.42 mg/kg BW (mean ± S.D.), respectively. The absorption of lidocaine following subcutaneous administration was rapid with Cmax and Tmax of 2.12 ± 0.81 µg/mL and 0.33 ± 0.11 h, respectively. The elimination half-lives (t½λz) of lidocaine hydrochloride and MGX were 1.71 ± 0.51 h and 3.19 ± 1.21 h, respectively. Injection of 1% lidocaine hydrochloride (0.5 mL/site) was safe and effective in blocking the nerves supplying horn buds in goat kids.

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