scholarly journals Milk and Blood Pharmacokinetics of Tylosin and Tilmicosin following Parenteral Administrations to Cows

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Tulay Avci ◽  
Muammer Elmas
Keyword(s):  
Peak Concentration ◽  
Subcutaneous Administration ◽  
Parenteral Administration ◽  
Intramuscular Administration ◽  
Withdrawal Period ◽  
Holstein Breed ◽  
Elimination Half ◽  
Time Required

The aim of this study is to determine the pharmacokinetics of tylosin and tilmicosin in serum and milk in healthy Holstein breed cows (n=12) and reevaluate the amount of residue in milk. Following the intramuscular administration of tylosin, the maximum concentrations (Cmax) in serum and milk were found to be1.30±0.24and4.55±0.23 µg/mL, the time required to reach the peak concentration (tmax) was found to be 2nd and 4th h, and elimination half-lives (t1/2β) were found to be20.46±2.08and26.36±5.55 h, respectively. Following the subcutaneous administration of tilmicosin, theCmaxin serum and milk were found to be0.86±0.20and20.16±1.13 µg/mL, thetmaxwas found to be 1st and 8th h, and thet1/2βwere found to be29.94±6.65and43.02±5.18 h, respectively.AUCmilk/AUCserumandCmax-milk/Cmax-serumrates, which are indicators for determining the rate of drugs that pass into milk, were, respectively, calculated as5.01±0.72and3.61±0.69for tylosin and23.91±6.38and20.16±1.13for tilmicosin. In conclusion, it may be stated that milk concentration of tylosin after parenteral administration is higher than expected like tilmicosin and needs more withdrawal period for milk than reported.

scholarly journals Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata, a Novel Anticoagulant Candidate, in Rats by Bioanalytical Methods

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 212
Author(s):  
Shuang Liu ◽  
Taocui Zhang ◽  
Huifang Sun ◽  
Lisha Lin ◽  
Na Gao ◽  
...  
Keyword(s):  
Peak Concentration ◽  
Bioanalytical Methods ◽  
Subcutaneous Administration ◽  
Parent Drug ◽  
Bleeding Risk ◽  
Rat Plasma ◽  
Preclinical Study ◽  
Time To Peak ◽  
Elimination Half ◽  
Plasma And Urine Samples

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (Tmax) was at about 1 h, and the peak concentration (Cmax) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(T1/2β) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.

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.

scholarly journals Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model: Impact of Area under the Curve/MIC Ratios on Eradication

2002 ◽  
Vol 46 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Philip D. Lister
Keyword(s):  
Streptococcus Pneumoniae ◽  
Peak Concentration ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Logarithmic Phase ◽  
Pharmacokinetic Models ◽  
Elimination Half ◽  
The Impact ◽  
Similar Peak

ABSTRACT Previous studies have demonstrated that fluoroquinolone area under the curve (AUC)/MIC ratios of 30 to 50 are sufficient to eradicate pneumococci from in vitro pharmacokinetic models (IVPMs). However, more systematic studies of the impact of AUC/MIC ratios on the antipneumococcal activities of fluoroquinolones are needed. In the present study, a two-compartment IVPM was used to evaluate the impact of AUC/MIC ratios on the pharmacodynamics of gatifloxacin against four strains of Streptococcus pneumoniae. Gatifloxacin MICs were 0.4 to 1 μg/ml, whereas levofloxacin MICs were 1.8 to 3.2 μg/ml. Since both peak concentration/MIC (peak/MIC) and AUC/MIC ratios affect fluoroquinolone pharmacodynamics, logarithmic-phase cultures (5 × 107 CFU/ml) were exposed to gatifloxacin at constant peak/MIC ratios of 2:1 to 3:1 at 0 and 24 h, elimination half-lives were varied to provide a range of AUC/MIC ratios, and changes in viable counts were measured over 30 h. As a comparison, levofloxacin was evaluated at similar peak/MIC ratios and at AUC/MIC ratios of 30 to 38. For each strain, killing rates through 4 to 8 h were similar since peak/MIC ratios were kept constant. However, continued killing and eradication were observed only when gatifloxacin AUC/MIC ratios were 27 to 48. Levofloxacin also provided eradication. In contrast, substantial regrowth was observed in most experiments when gatifloxacin AUC/MIC ratios were 9 to 24. These data provide further support that fluoroquinolone AUC/MIC ratios of approximately 30 or higher can be sufficient for eradication of pneumococci from IVPMs. Furthermore, the overall impact of the AUC/MIC ratio was not influenced by the strain evaluated or its susceptibility to gatifloxacin. Further studies with other fluoroquinolones and pneumococci that exhibit wider ranges of susceptibilities are warranted. In addition, similar studies with higher peak/MIC ratios are needed to better define the impact of AUC/MIC ratios and peak/MIC ratios on the antipneumococcal pharmacodynamics of fluoroquinolones.

Clearance of Continuous Intravenous Morphine for Severe Cancer Pain

1987 ◽  
Vol 21 (12) ◽  
pp. 981-985
Author(s):  
Marc L. Citron ◽  
John R. Reynolds ◽  
Wen-Nuei Lin ◽  
Peter D. Frade ◽  
Mark Schemansky ◽  
...  
Keyword(s):  
Steady State ◽  
Cancer Pain ◽  
Cancer Patients ◽  
Intractable Pain ◽  
Time Period ◽  
Elimination Half ◽  
Steady State Serum ◽  
Intravenous Morphine ◽  
High Doses ◽  
Time Required

Four cancer patients with intractable pain received continuous morphine infusions in doses of 15–275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of ≤ 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted.

The Pharmacokinetics of Etanercept in Healthy Volunteers

2000 ◽  
Vol 34 (2) ◽  
pp. 161-164 ◽  
Author(s):  
Joan M Korth-Bradley ◽  
Abbe Sue Rubin ◽  
Roberta K Hanna ◽  
Donna K Simcoe ◽  
Mary E Lebsack
Keyword(s):  
Healthy Volunteers ◽  
Subcutaneous Injection ◽  
Peak Concentration ◽  
Subcutaneous Administration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Serum Samples ◽  
Drug Concentrations ◽  
Apparent Clearance

OBJECTIVE: To describe the pharmacokinetics of etanercept when administered by subcutaneous injection in single doses to healthy volunteers. METHODS: Twenty-six healthy volunteers between 19 and 50 years of age received single doses of etanercept 25 mg by subcutaneous injection into the abdomen. Serial serum samples were collected for 21 days. An enzyme-linked immunosorbent assay with a quantitation limit of 0.3 ng/mL was used to measure the drug concentrations. RESULTS: Etanercept was well tolerated by healthy volunteers. A one-compartment model was found to best describe the concentration–time data and was used to determine the pharmacokinetic parameters. Etanercept is slowly absorbed from the site of injection with a time of peak concentration (± SD) of 51 ± 14 hours; peak concentration was 1.46 ± 0.72 mg/L. The AUC was 235 ± 98 mg•h/L, apparent clearance was 132 ± 85 mL/h, apparent volume of distribution was 12 ± 6 L, and the half-life was 68 ± 19 hours. CONCLUSIONS: Etanercept was slowly absorbed and slowly eliminated after subcutaneous administration. Dosing at the recommended rate of 25 mg twice weekly would be expected to result in concentrations of approximately 3 mg/L. Intersubject variability for apparent clearance in healthy volunteers was 64%.

PHARMACOKINETICS OF EN0XAPARIN AFTER SINGLE SUBCUTANEOUS ADMINISTRATION OF INCREASING DOSES (20 UP TO 80 MG) TO HEALTHY VOLUNTEERS

1987 ◽  
Author(s):  
L Bara ◽  
Y Le Roux ◽  
M Woler ◽  
F Chauliac ◽  
A Frydman ◽  
...  
Keyword(s):  
Subcutaneous Administration ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Thrombin Time ◽  
Mean Values ◽  
Elimination Half ◽  
Heparin Plasma ◽  
The Mean ◽  
The One ◽  
Apparent Volume Of Distribution

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.

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

1998 ◽  
Vol 42 (2) ◽  
pp. 289-292 ◽  
Author(s):  
B. Nouaille-Degorce ◽  
C. Veau ◽  
S. Dautrey ◽  
M. Tod ◽  
D. Laouari ◽  
...  
Keyword(s):  
Renal Failure ◽  
Intestinal Secretion ◽  
Parenteral Administration ◽  
Compensatory Mechanisms ◽  
Time Curve ◽  
Mixed Effect ◽  
Nonlinear Mixed Effect Model ◽  
Nonlinear Mixed Effect ◽  
Effect Model ◽  
Elimination Half

ABSTRACT Ciprofloxacin pharmacokinetics have been shown to be modified in patients with renal failure (e.g., the intestinal secretion of ciprofloxacin is increased). This study investigated the influence of renal failure on the pharmacokinetics of ciprofloxacin following oral and parenteral administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CLR) was reduced in nephrectomized rats (5.3 ± 1.4 versus 17.8 ± 4.7 ml/min/kg, P< 0.01, nephrectomized versus control rats). However, nonrenal clearance was increased in nephrectomized rats (32 ± 4 versus 15 ± 5 ml/min/kg, P < 0.01, nephrectomized versus control rats), suggesting compensatory mechanisms for reduced renal function. After oral administration, apparent total clearance and CLR were reduced (P < 0.01) in nephrectomized rats (117 ± 25 and 6.8 ± 4.4 ml/min/kg, respectively) compared with the values for control rats (185 ± 9 and 22.6 ± 5.3 ml/min/kg, respectively) and the area under the concentration-time curve was higher (P < 0.01) for nephrectomized rats (436.3 ± 90.5 mg · min/liter) than for control rats (271.3 ± 14.3 mg · min/liter). Terminal elimination half lives in the two groups remained constant after oral and parenteral administration. These results suggest an increased bioavailability of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.

Clozapine Intoxication in a Dog

2002 ◽  
Vol 38 (5) ◽  
pp. 421-424
Author(s):  
Boel A. Fransson ◽  
Katrina A. Mealey ◽  
Sarah R. Dutta
Keyword(s):  
Supportive Care ◽  
Half Life ◽  
Peak Concentration ◽  
Clinical Signs ◽  
Serum Levels ◽  
Auditory Stimulation ◽  
Successful Outcome ◽  
Elimination Half Life ◽  
Elimination Half

Intoxication with clozapine in a dog, suspected from history and clinical signs at presentation, was confirmed by demonstration of decreasing serum levels of this drug. Clozapine is a tricyclic dibenzodiazepine used for treatment of human schizophrenia, and clinical signs of intoxication in humans include tachycardia, seizures, muscle fasciculations, agitation, and sialorrhea. This dog showed ptyalism, hyperthermia, tachycardia, and was easily excited by tactile or auditory stimulation. The calculated peak concentration of clozapine in this dog was approximately 6,000 ng/mL, and the elimination half-life (t1/2) was 5 hours. Charcoal administration and supportive care led to a successful outcome in this patient.

scholarly journals Pharmacokinetics and Tissue Penetration of Linezolid following Multiple Oral Doses

2001 ◽  
Vol 45 (6) ◽  
pp. 1843-1846 ◽  
Author(s):  
Thekli Gee ◽  
Richard Ellis ◽  
Gillian Marshall ◽  
Jenny Andrews ◽  
Janet Ashby ◽  
...  
Keyword(s):  
Peak Concentration ◽  
Blister Fluid ◽  
Healthy Male ◽  
Tissue Penetration ◽  
Final Dose ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
Oral Doses ◽  
Mean Time

ABSTRACT The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 μg/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 μg/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) μg · h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.

scholarly journals Artemether Bioavailability after Oral or Intramuscular Administration in Uncomplicated Falciparum Malaria

2003 ◽  
Vol 47 (12) ◽  
pp. 3795-3798 ◽  
Author(s):  
Kamolrat Silamut ◽  
Paul N. Newton ◽  
Paktiya Teja-Isavadharm ◽  
Yupin Suputtamongkol ◽  
Duangsuda Siriyanonda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Acute Phase ◽  
Peak Concentration ◽  
Antimalarial Activity ◽  
Acute Illness ◽  
Intramuscular Administration ◽  
Time Curve ◽  
Convalescent Phase ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

ABSTRACT The antimalarial activity of artemether following oral or intramuscular administration in the plasma of 15 adults with acute uncomplicated Plasmodium falciparum malaria was measured by bioassay. The peak concentrations in plasma following oral administration were higher in patients with acute illness (median, 1,905 mmol of dihydroartemisinin [DHA] equivalents per liter; range, 955 to 3,358 mmol of DHA equivalents per liter) than in patients in the convalescent phase (median, 955 mmol of DHA equivalents per liter; range, 576 to 1,363 mmol of DHA equivalents per liter), and clearance (CL/F) was lower in patients in the acute phase (1.11 liters/kg/h; range, 0.21 to 3.08 liters/kg/h) than in patients in the convalescent phase (median, 2.76 liters/kg/h; range, 1.56 to 5.74 liters/kg/h) (P ≤ 0.008). Antimalarial activity in terms of the peak concentration in plasma (C max) after oral administration was a median of 16 times higher than that after intramuscular administration. The ratio of the area under the plasma concentration-time curve during the first 24 h (AUC0-24) after oral administration of artemether to the AUC0-24 after intramuscular administration was a median of 3.3 (range, 1 to 11) (P = 0.0001). In the acute phase, the time to C max was significantly shorter after oral administration (median, 1 h; range, 0.5 to 3.0 h) than after intramuscular administration (median, 8 h; range, 4 to 24 h) (P = 0.001). Intramuscular artemether is absorbed very slowly in patients with acute malaria.

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