scholarly journals The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model

2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Kevin C. Worley ◽  
Scott W. Roberts ◽  
Roger E. Bawdon
Keyword(s):  
Active Metabolite ◽  
Ex Vivo ◽  
Reference Method ◽  
Human Model ◽  
Transplacental Passage ◽  
Oseltamivir Carboxylate ◽  
Ex Vivo Model ◽  
Transplacental Transfer ◽  
Perfusion Studies ◽  
Oseltamivir Phosphate

Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete.Objective. To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model.Study Design. Perfusion studies were performed in six placentas from term, uncomplicated deliveries. Concentrations of oseltamivir phosphate (OP) that were 5-6 fold, 20–30 fold, and 600–800 fold above the therapeutic peak were tested, as neither OP nor its active metabolite, oseltamivir carboxylate (OC), could be detected at near-therapeutic concentrations. The transplacental transfer and accumulation of OC were assessed using the antipyrine reference method.Results. OP was extensively metabolized to OC. In the 4 placentas with the highest concentration of OP, OC had a mean clearance index of , suggesting that transplacental passage occurs at a relatively low rate. Measurable fetal accumulation occurred in the two placentas with the highest initial concentrations.Conclusions. Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal.

scholarly journals Barusiban, a selective oxytocin receptor antagonist: placental transfer in rabbit, monkey, and human†

2020 ◽  
Vol 103 (1) ◽  
pp. 135-143
Author(s):  
Hanns Helmer ◽  
Leila Saleh ◽  
Ljubomir Petricevic ◽  
Martin Knöfler ◽  
Torsten M Reinheimer
Keyword(s):  
Cynomolgus Monkey ◽  
Placental Transfer ◽  
Ex Vivo ◽  
Oxytocin Receptor ◽  
Human Model ◽  
Ex Vivo Model ◽  
Fetal Plasma ◽  
V1a Receptor ◽  
Fetal Tissues ◽  
Species Specific

Abstract The use of drugs in pregnancy always raises concerns regarding potential fetal exposure and possible adverse effects through their accumulation in fetal tissues and organs. Barusiban is an oxytocin antagonist under development for potential use as tocolytic in preterm-labor patients. It displays greater affinity for the oxytocin receptor compared to vasopressin V1A receptor and would thus not interfere with vasopressin-induced effects of the V1A receptor. Barusiban placental transfer was determined in the rabbit and cynomolgus monkey and in an ex vivo human cotyledon model. In the rabbit, there was an approximately 5% transfer of barusiban from the maternal to the fetal blood, without significant accumulation in any of the investigated fetal tissues. In the cynomolgus monkeys, the mean fetal plasma barusiban concentration was 9.1% of the maternal level. This was similar to the percentage of barusiban transfer in the human placental single cotyledon, which once equilibrated ranged between 9.3 and 11.0% over the observation period. The transfer of the small-molecule antipyrine as a comparator in this human model was approximately three times greater. The similarity in the degree of transfer in the cynomolgus monkey and human cotyledon, while being less in the rabbit, may reflect the species-specific placental barrier structure between the maternal and fetal compartments. In conclusion, limited placental transfer of barusiban occurred in all three models. The similarity of barusiban transfer in the cynomolgus and the human placental single cotyledon suggests the latter ex vivo model to be useful in assessing future drug candidates to be used in pregnant women.

1849: Systematic Evaluation of 21μm Thulium Laser Device for Treatment of Benign Prostatic Enlargement in an Ex-VIVO Model

2007 ◽  
Vol 177 (4S) ◽  
pp. 614-614 ◽  
Author(s):  
Gunnar Wendt-Nordahl ◽  
Stefanie Huckele ◽  
Patrick Honeck ◽  
Peter Aiken ◽  
Thomas Knoll ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Systematic Evaluation ◽  
Thulium Laser ◽  
Laser Device ◽  
Benign Prostatic Enlargement ◽  
Ex Vivo Model ◽  
Prostatic Enlargement

Porcine small intestine, a good ex vivo model to investigate absorption and metabolism of natural products

2017 ◽  
Author(s):  
J Houriet ◽  
YE Arnold ◽  
C Petit ◽  
YN Kalia ◽  
JL Wolfender
Keyword(s):  
Natural Products ◽  
Small Intestine ◽  
Ex Vivo ◽  
Ex Vivo Model

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.

EMR+: Vorstellung einer neuen endoskopischen Resektionsmethode im ex-vivo Model

2019 ◽  
Author(s):  
RF Knoop ◽  
E Wedi ◽  
V Ellenrieder ◽  
A Neesse ◽  
S Kunsch
Keyword(s):  
Ex Vivo ◽  
Ex Vivo Model

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Cartilage Explants ◽  
Ex Vivo Model ◽  
Chondrocyte Viability ◽  
Platelet Concentration ◽  
The Absolute ◽  
Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

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