scholarly journals Pharmacokinetic profiles of levofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits (Oryctolagus cuniculus)

2020 ◽  
Vol 21 (2) ◽  
Author(s):  
Andrejs Sitovs ◽  
Laura Voiko ◽  
Dmitrijs Kustovs ◽  
Liga Kovalcuka ◽  
Dace Bandere ◽  
...  
Keyword(s):  
Oryctolagus Cuniculus ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Profiles

scholarly journals Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats

2020 ◽  
Vol 13 (9) ◽  
pp. 231
Author(s):  
Seung-Hyun Jeong ◽  
Ji-Hun Jang ◽  
Yong-Bok Lee
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Phase ◽  
Routes Of Administration ◽  
Administration Routes ◽  
Pharmacokinetic Profiles

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.

Peripheres keratinisierendes Ameloblastom bei einem Zwergkaninchen (Oryctolagus cuniculus f. dom.)

2014 ◽  
Vol 42 (05) ◽  
pp. 331-335 ◽  
Author(s):  
I. Völker ◽  
P. Kammeyer ◽  
B. Hinzmann ◽  
D. Lüerssen ◽  
W. Baumgärtner ◽  
...  
Keyword(s):  
Oryctolagus Cuniculus ◽  
Odontogene Tumoren

ZusammenfassungEin 3,5 Jahre altes, männlich-kastriertes Zwergkaninchen wurde mit einer vorberichtlich schnell wachsenden Umfangsvermehrung in der Gingiva des Oberkiefers vorgestellt. Die Neubildung wurde vollständig chirurgisch exzidiert. Histopathologisch ließ sich ein expansiv wachsendes, multilobuläres, teils zystisches, peripheres keratinisierendes Ameloblastom nachweisen. Die immunhistologische Phänotypisierung der Tumorzellen ergab eine zytoplasmatische Markierung mit verschiedenen Panzytokeratin-Antikörpern. Graduell variabel wurden die Zytokeratine 5/6, 7, 10 und 14 exprimiert. Zytokeratin 20 war nicht nachweisbar. Vimentin wurde im Zytoplasma von mesenchymalen Zellen des Stromas exprimiert. Außerdem wurde im Kern von ca. 10% der Tumorzellen das Protein des Tumorsuppressorgens p53 und in ca. 5% der Proliferationsmarker Ki67 festgestellt. Odontogene Tumoren sollten bei Kaninchen mit Umfangsvermehrungen am Kiefer differenzialdiagnostisch berücksichtigt werden.

Anticoagulant Activity of Hirulog™, a Direct Thrombin Inhibitor, in Humans

1993 ◽  
Vol 69 (02) ◽  
pp. 157-163 ◽  
Author(s):  
Irving Fox ◽  
Adrian Dawson ◽  
Peter Loynds ◽  
Jane Eisner ◽  
Kathleen Findlen ◽  
...  
Keyword(s):  
Rational Design ◽  
Therapeutic Potential ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Direct Thrombin Inhibitor ◽  
Controlled Study ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Thrombotic Disease ◽  
Dose Dependent

SummaryHirulog™ (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095–101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers.In a randomized, placebo-controlled study (n = 54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 1 kg−1 h−1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p <0.001) and subcutaneous administration (r = 0.7, p = 0.002).To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide’s activity. At the administered dose of 0.6 mg kg−1 h−1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.The final phase of the study examined the activity and tolerability of hirulog in ten subjects during prolonged intravenous infusions for up to 24 h. The peptide (0.3 mg kg−1 h−1) exhibited sustained anticoagulant activity with no evidence for a cumulative effect. During hirulog infusion, APTT was prolonged from 210 to 250% baseline.In all phases of the study, hirulog administration was generally well-tolerated.Our observations show that hirulog is an active antithrombin agent with excellent tolerability in humans. As a direct thrombin inhibitor, hirulog provides a novel approach for the management of thrombotic disease.

Platelet Intracellular Calcium Is not Modified by Subcutaneous Administration of Erythropoietin

1994 ◽  
Vol 72 (02) ◽  
pp. 326-327
Author(s):  
Claudia Lo Cascio ◽  
Patrizia Guzzo ◽  
Carmelo Loschiavo ◽  
Franco Manzato ◽  
Clara Lechi
Keyword(s):  
Intracellular Calcium ◽  
Subcutaneous Administration

Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

1995 ◽  
Vol 73 (02) ◽  
pp. 219-222 ◽  
Author(s):  
Manuel Monreal ◽  
Luis Monreal ◽  
Rafael Ruiz de Gopegui ◽  
Yvonne Espada ◽  
Ana Maria Angles ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
In Vitro Study ◽  
Ex Vivo Model ◽  
Suitable Candidate ◽  
Significant Prolongation ◽  
High Doses ◽  
Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

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