scholarly journals Pharmacokinetic studies of 1.ALPHA., 24(R)-(OH)2D3(TV-02)(2). Plasma level, distribution, metabolism and excretion after repeated subcutaneous administration to rats.

1990 ◽  
Vol 5 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Tomohiro OHTA ◽  
Masaru YAMAMOTO ◽  
Hirohide MIMURA ◽  
Takashi MATSUNAGA ◽  
Mamoru KIYOKI ◽  
...  
Keyword(s):  
Plasma Level ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Studies

scholarly journals Pharmacokinetic studies of 1.ALPHA., 24(R)-(OH)2D3(TV-02)(1). Plasma level, distribution metabolism and excretion after a single subcutaneous administration to rats.

1990 ◽  
Vol 5 (1) ◽  
pp. 3-23 ◽  
Author(s):  
Tomohiro OHTA ◽  
Yoshinori TAKADA ◽  
Hirohide MIMURA ◽  
Masaru YAMAMOTO ◽  
Takashi MATSUNAGA ◽  
...  
Keyword(s):  
Plasma Level ◽  
Subcutaneous Administration ◽  
Pharmacokinetic 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 Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration.

1992 ◽  
Vol 2 (9) ◽  
pp. 1405-1416
Author(s):  
A Besarab ◽  
K K Flaharty ◽  
A J Erslev ◽  
J B McCrea ◽  
P H Vlasses ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Subcutaneous Administration ◽  
Entire Group ◽  
Pharmacokinetic Studies ◽  
Weekly Dose ◽  
Recombinant Erythropoietin ◽  
Dialysis Patients ◽  
Human Recombinant Erythropoietin ◽  
Human Erythropoietin ◽  
Stage Renal Disease

The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.

scholarly journals Pharmacokinetic studies of 1.ALPHA.,24(R)-(OH)2D3(TV-02)(5). Plasma level and excretion in beagle dogs.

1990 ◽  
Vol 5 (1) ◽  
pp. 63-69
Author(s):  
Tomohiro OHTA ◽  
Hirohide MIMURA ◽  
Masaru YAMAMOTO ◽  
Mamoru KIYOKI ◽  
Takeo OHBA ◽  
...  
Keyword(s):  
Plasma Level ◽  
Pharmacokinetic Studies ◽  
Beagle Dogs

scholarly journals In Vivo Pharmacodynamic Characterization of a Novel Odilorhabdin Antibiotic, NOSO-502, against Escherichia coli and Klebsiella pneumoniae in a Murine Thigh Infection Model

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Miao Zhao ◽  
Alexander J. Lepak ◽  
Karen Marchillo ◽  
Jamie VanHecker ◽  
David R. Andes
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Subcutaneous Administration ◽  
Dose Fractionation ◽  
Infection Model ◽  
Pharmacokinetic Studies ◽  
Time Curve ◽  
Content Type ◽  
The Mean

ABSTRACT NOSO-502 is a novel odilorhabdin antibiotic with potent activity against Enterobacteriaceae. The goal of these studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) indices and magnitude best correlated with efficacy in the murine thigh infection model. Six Escherichia coli and 6 Klebsiella pneumoniae isolates were utilized. MICs were determined using CLSI methods and ranged from 1 to 4 mg/liter. A neutropenic murine thigh infection model was utilized for all treatment studies. Single-dose plasma pharmacokinetics were determined in mice after subcutaneous administration of 7.81, 31.25, 125, and 500 mg/kg of body weight. Pharmacokinetic studies exhibited peak concentration (Cmax) values of 1.49 to 84.6 mg/liter, area under the concentration-time curve from 0 h to infinity (AUC0–∞) values of 1.94 to 352 mg · h/liter, and beta elimination half-lives of 0.41 to 1.1 h. Dose fractionation studies were performed using total drug doses of 7.81 mg/kg to 2,000 mg/kg fractionated into regimens of every 3 h (q3h), q6h, q12h, or q24h. Nonlinear regression analysis demonstrated that AUC/MIC was the PK/PD parameter that best correlated with efficacy (R2, 0.86). In subsequent studies, we used the neutropenic murine thigh infection model to determine the magnitude of NOSO-502 AUC/MIC needed for the efficacy against a diverse group of Enterobacteriaceae. Mice were treated with 4-fold-increasing doses (range, 3.91 to 1,000 mg/kg) of NOSO-502 every 6 h. The mean 24-h free-drug AUC/MIC (fAUC)/MIC) magnitudes associated with net stasis and 1-log kill endpoint for K. pneumoniae were 4.22 and 17.7, respectively. The mean fAUC/MIC magnitude associated with net stasis endpoint for E. coli was 10.4. NOSO-502 represents a promising novel, first-in-class odilorhabdin antibiotic with in vivo potency against Enterobacteriaceae.

In Vivo Inhibition Of Thromboxane A2-Synthetase : Protective Effect Against Collagen And Arachidonate Infusion

1981 ◽  
Author(s):  
D Sincholle ◽  
C Fontaine ◽  
B Martin ◽  
C Bonne ◽  
P Regnault
Keyword(s):  
Blood Pressure ◽  
Plasma Level ◽  
Oral Treatment ◽  
Lethal Dose ◽  
Thromboxane A2 ◽  
Pharmacokinetic Studies ◽  
Antithrombotic Drugs ◽  
Thromboxane Synthetase ◽  
Derivatives Of

Rabbits and rats anaesthetised with thiopental were infused intravenously either with sodium arachidonate or collagen. Blood pressure and pneumogram were recorded and Thromboxane B2 (T×B2) plasma level was measured prior and after infusion. The aggregating agents elicited hypotension, respiratory break down and killed the animals. These events were associated with an increase in plasma T×B2 concentration. Intraperitoneal pretreatment of animals with derivatives of imidazole (1 -(3-hydroxy-1-oct enyl)-imidazole , chlorhydrat e (CBS6l2) and its nicotinic ester (CBS634) delayed toxic effects and death. In the standard conditions used in this study, the lethal dose of arachidonate in the rabbit was 8.4 t 1.0 mg/kg. This dose was increased to 21.6 ± 4.3 and 50.4 ± 8.0 when the animals were pretreated with CBS6l2 at the dose of respectively 12.5 mg/kg and 25 mg/kg. In the same way, the lethal dose of collagen in the rat was 0.5 ± 0.1 mg/kg in controls and 1.2 t 0.1 mg/kg after treatment with thromboxane-synthetase inhibitor (CBS634 = 25 mg/kg). The lethal dose of collagen was correlated to the concentration of T×B2 formed in the blood (controls : 4.4 ± 0.3 ; treated : 1.7 ± 0.2 ng/ml).Potential interest of these antithrombotic drugs could be strengthened by further pharmacokinetic studies after oral treatment actually in progress.

Subcutaneous Administration of Amifostine During Fractionated Radiotherapy: A Randomized Phase II Study

2000 ◽  
Vol 18 (11) ◽  
pp. 2226-2233 ◽  
Author(s):  
Michael I. Koukourakis ◽  
George Kyrias ◽  
Stelios Kakolyris ◽  
Charalambos Kouroussis ◽  
Chryssi Frangiadaki ◽  
...  
Keyword(s):  
Phase Ii ◽  
Subcutaneous Administration ◽  
Intravenous Route ◽  
Pharmacokinetic Studies ◽  
Subcutaneous Route ◽  
Fractionated Radiotherapy ◽  
Flat Dose ◽  
Randomized Phase Ii ◽  
Perineal Skin ◽  
Grade 3

PURPOSE: Amifostine (WR-2721) is an impotant cytoprotective agent. Although intravenous administration is the standard route, pharmacokinetic studies have shown acceptable plasma levels of the active metabolite of amifostine (WR-1605) after subcutaneous administration. The subcutaneous route, due to its simplicity, presents multiple advantages over the intravenous route when amifostine is used during fractionated radiotherapy. PATIENTS AND METHODS: Sixty patients with thoracic, 40 with head and neck, and 40 with pelvic tumors who were undergoing radical radiotherapy were enrolled onto a randomized phase II trial to assess the feasibility, tolerance, and cytoprotective efficacy of amifostine administered subcutaneously. A flat dose of amifostine 500 mg, diluted in 2.5 mL of normal saline, was injected subcutaneously 20 minutes before each radiotherapy fraction. RESULTS: The subcutaneous amifostine regimen was well tolerated by 85% of patients. In approximately 5% of patients, amifostine therapy was interrupted due to cumulative asthenia, and in 10%, due to a fever/rash reaction. Hypotension was never noted, whereas nausea was frequent. A significant reduction of pharyngeal, esophageal, and rectal mucositis was noted in the amifostine arm (P < .04). The delays in radiotherapy because of grade 3 mucositis were significanly longer in the group of patients treated with radiotherapy alone (P < .04). Amifostine significantly reduced the incidence of acute perineal skin and bladder toxicity (P < .0006). CONCLUSION: Subcutaneous administration of amifostine is well tolerated, effectively reduces radiotherapy’s early toxicity, and prevents delays in radiotherapy. The subcutaneous route is much simpler and saves time compared with the intravenous route of administration and can be safely and effectively applied in the daily, busy radiotherapy practice.

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