Comparison of systemic exposure to nemifitide following two methods of subcutaneous administration to healthy volunteers

2005 ◽  
Vol 26 (9) ◽  
pp. 379-385 ◽  
Author(s):  
G. Nicolau ◽  
J.P. Feighner ◽  
R. Stout ◽  
J. Hlavka ◽  
M. Gutierrez ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Subcutaneous Administration ◽  
Systemic Exposure

Changes in morphine analgesia and side effects during daily subcutaneous administration in healthy volunteers

Pain ◽  
2008 ◽  
Vol 137 (2) ◽  
pp. 395-404 ◽  
Author(s):  
Karin Lottrup Petersen ◽  
Thomas Meadoff ◽  
Scott Press ◽  
Michelle M. Peters ◽  
Matthew D. LeComte ◽  
...  
Keyword(s):  
Side Effects ◽  
Healthy Volunteers ◽  
Subcutaneous Administration ◽  
Morphine Analgesia

scholarly journals Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial

2020 ◽  
Vol 75 (9) ◽  
pp. 2650-2656 ◽  
Author(s):  
Peter Matzneller ◽  
Perrin Ngougni Pokem ◽  
Arnaud Capron ◽  
Edith Lackner ◽  
Beatrix Wulkersdorfer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Protein Binding ◽  
Healthy Volunteers ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Soft Tissues ◽  
Therapeutic Option ◽  
Subcutaneous Administration ◽  
Intravenous Route ◽  
Drug Concentrations

Abstract Background The antibiotic temocillin has recently been rediscovered as a promising therapeutic option against MDR Gram-negative bacteria. However, some aspects of the pharmacokinetic (PK) profile of the drug are still to be elucidated: subcutaneous administration of temocillin might be of interest as an alternative to the intravenous route in selected patients. Similarly, information on the penetration of temocillin into human soft tissues is lacking. Objectives To investigate the feasibility and plasma PK of subcutaneous dosing as well as soft tissue PK of temocillin after intravenous administration to healthy volunteers. Methods Eight healthy volunteers received 2 g of temocillin both as intravenous and subcutaneous infusion in a randomized two-period crossover study. Concentration–time profiles of total temocillin in plasma (after both routes) and of unbound temocillin in plasma, muscle and subcutis (only after intravenous dosing) were determined up to 12 h post-dose. Results Subcutaneous dosing caused some infusion site discomfort but resulted in sustained drug concentrations over time with only slightly decreased overall exposure compared with intravenous dosing. Plasma protein binding of temocillin showed concentration-dependent behaviour and was higher than previously reported. Still, unbound drug concentrations in muscle and subcutis determined by microdialysis markedly exceeded those in plasma, suggesting good tissue penetration of temocillin. Conclusions The subcutaneous administration of temocillin is a valid and feasible alternative to intravenous dosing. With the description of plasma protein binding and soft tissue PK of temocillin in healthy volunteers, this study provides important information that adds to the ongoing characterization of the PK profile of temocillin and might serve as input for PK/PD considerations.

PHARMACOKINETICS OF A LOW MOLECULAR WEIGHT HEPARIN (KABI 2165, FRAGMIN) ATFER INTRAVENOUS AND SUBCUTANEOUS ADMINISTRATION IN HUMAN VOLUNTEERS AND ITS IN VIVO NEUTRALIZATION BY PROTAMINE SULFATE

1987 ◽  
Author(s):  
J Albada ◽  
K K Nieuwenhuis ◽  
J J Sixma
Keyword(s):  
Molecular Weight ◽  
Healthy Volunteers ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Subcutaneous Administration ◽  
Low Molecular Weight ◽  
Protamine Sulphate ◽  
Original Curve ◽  
Rebound Phenomenon

Pharmacokinetics of a low molecular weight heparin (LMWH) were studied in healthy volunteers. After an intravenous bolus injection of 5000 anti-Xa U in 5 healthy volunteers anti Xa activity disappeared according to the combination of saturable and a linear mechanism, preceded by a rapid initial disappearance. The apparent half-life of the anti Xa activity is about twice as long as that of standard heparin. In another set of experiments 5000 anti Xa U of LMWH were immediately followed by 50 mgr of Protamine Sulphate (PS). The curve of the anti Xa-activity parallelled the original curve at a level of about 30-40%. No rebound phenomenon was observed. The same dose of the LMWH followed by 100 mg of PS resulted in an anti Xa disappearance curve at an obvious higher level of about 50%. Also at this dose no rebound phenomenon was noticed.A continuous infusion of 10.000 anti Xa U/24 h during 10 hours was followed by 15.000 anti Xa U/24 h for another 10 hours after which the dose was raised to 20.000 anti Xa U/24 h for another 10 hours. Only the first infusion period resulted in a plateau fase. At the end of these experiments anti Xa activity was neutralized by 50 mg P.S. i.v. resulting in the disappearance of less than 50% of anti Xa activity. After subcutaneous administration of 15.000 anti Xa U (corresponding to the dose for i.v. treatment per day with this LMWH) peak levels of 1,1-1,8 anti Xa were reached after 3-4 hours. Supra-optimal anti Xa levels (higher than 0.9) were observed in all volunteers during a period of 5 hours. After 24 hours in none of the volunteers any anti Xa-activity could be detected.Conclusions:In contrast to previous reports pharmacokinetics of this LMWH do not essentially differ from those of standard heparin apart from its longer half-life and its high bioavialability after subcutaneous injection.

scholarly journals Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3885-3894 ◽  
Author(s):  
M de Haas ◽  
JM Kerst ◽  
CE van der Schoot ◽  
J Calafat ◽  
CE Hack ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Plasma Levels ◽  
Subcutaneous Administration ◽  
Secretory Vesicles ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Specific Granules ◽  
Stimulating Factor

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.

Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers

2002 ◽  
Vol 58 (8) ◽  
pp. 515-520 ◽  
Author(s):  
Hege Christensen ◽  
Anders �sberg ◽  
Aase-Britt Holmboe ◽  
Knut Berg
Keyword(s):  
Healthy Volunteers ◽  
Grapefruit Juice ◽  
Systemic Exposure

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%.

scholarly journals Safety evaluation of the interchangeable use of robenacoxib in commercially-available tablets and solution for injection in cats

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Mark C. Heit ◽  
L. Jay Stallons ◽  
Wolfgang Seewald ◽  
Caryn M Thompson ◽  
Céline E. Toutain ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Day Treatment ◽  
Oral Treatment ◽  
Subcutaneous Administration ◽  
Systemic Exposure ◽  
Control Group ◽  
Serious Adverse Events ◽  
Blood Concentrations ◽  
Daily Dose

Abstract Background Robenacoxib (Onsior™) is a non-steroidal anti-inflammatory drug developed for canine and feline use for the control of pain and inflammation. It is available as both tablets and solution for injection. The objective of this study was to evaluate the safety of the interchangeable use of commercially available robenacoxib formulations when administered to cats orally using 6 mg tablets and subcutaneously using a solution for injection containing 20 mg/mL. Thirty-four naïve healthy 4-month old cats were enrolled in this 37-day study and were randomized to four groups (three robenacoxib and one control). One robenacoxib group received the maximum recommended dose (MRD) rate of each formulation, while the other two received two and three times this dose rate. The cats underwent three 10-day treatment cycles comprised of seven days of once daily oral administration followed by three days of subcutaneous administration. The third cycle was followed by an additional seven days of oral treatment. The control group received oral empty gelatin capsules or subcutaneous saline injections. Assessment of safety was based on general health observations, clinical observations, physical, ophthalmic, electrocardiographic and neurological examinations, clinical pathology evaluations, food consumption, body weight, and macroscopic and microscopic examinations. Blood samples were collected for toxicokinetic evaluation. Results Blood concentrations of robenacoxib confirmed systemic exposure of all treated cats. All cats were in good health through study termination and there were no serious adverse events during the study. There were no changes in body weight, food consumption, ophthalmic, physical or neurological examinations during the study. Treatment-related abnormalities were of low occurrence at all doses and included injection site changes (transient edema with minimal or mild, subacute/chronic inflammation histologically) and prolongation of the QT interval. These findings were consistent with previously observed findings in studies with robenacoxib administered separately orally or subcutaneously in cats. Thus, there were no adverse effects that could be attributed specifically to the interchangeable use of oral and injectable robenacoxib. Conclusions This 37-day laboratory study supports the safety of interchanging robenacoxib injection at a daily dose of 2 mg/kg with robenacoxib tablets at a daily dose of 1 mg/kg, or vice versa.

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