scholarly journals Pharmacokinetic Interactions between Concomitantly Administered Phenytoin with Rivaroxaban

Author(s):  
Y. Karnakar Reddy ◽  
T. Ramamohan Reddy

In the present investigation it was aimed to evaluate any possible pharmacokinetic interactions between Phenytoin and Rivaroxaban. Study was conducted in Male Wistar rats; animals were divided into three groups. Group 1 received Phenytoin alone, Group 2 received Rivaroxaban alone and Group 3 received Phenytoin and Rivaroxaban concomitantly. The treatment was given for 8 days and the blood samples were collected on day 1 and day 8. The samples were analyzed by HPLC. The results were showed no significant difference in the Pharmacokinetic parameters of Phenytoin in presence of Rivaroxaban. Whereas Rivaroxaban showed significant decrease in both Cmax and tmax in combination with Phenytoin. Phenytoin is a combined-gp inducer and strong CYP3A4 inducer therefore it may induce the metabolism of Rivaroxaban so it reduces the concentrations and increase the elimination rate. Based on the results obtained from pharmacokinetic study it was evident that the single dose of Rivaroxaban in combination with Phenytoin shows statistically significant interactions in its pharmacokinetic parameters.

2006 ◽  
Vol 14 (4) ◽  
pp. 238-241 ◽  
Author(s):  
Juliane Guimarães de Carvalho ◽  
Rodrigo Cardoso de Oliveira ◽  
Marília Afonso Rabelo Buzalaf

OBJECTIVE: This study evaluated the use of plasma, bone surface (periosteal) and whole bone as biomarkers of chronic fluoride (F) exposure. METHODS: Forty male Wistar rats were assigned to 4 groups (n=10/gr) that differed according to the F concentration they received in the drinking water. Groups 1, 2, 3 and 4 received water containing 0 (control), 5, 15, and 50 mg F/L, respectively. The rats were killed at 120 days of age. Plasma and femur were collected and analyzed for fluoride with the ion specific electrode by the direct method or after hexamethyldisiloxane-facilitated diffusion. Data were tested for statistically significant differences by ANOVA and linear regression (p<0.05). RESULTS: Mean (± SE) plasma F concentrations ranged from 0.030 ± 0.002 to 0.187 ± 0.013 (mg/mL). The concentrations in surface and whole bone ranged from 610 ± 32 to 4,693 222; and 647 ± 22 to 3,439 ± 134 µg/g, respectively. The surface/whole F concentration ratios were 0.941, 1.414, 1.173 and 1.377, for groups 1, 2, 3 and 4 respectively. For plasma and whole bone, the difference among all groups was statistically significant, except for group 2 compared to group 1. For bone surface, all groups differed from each other except for group 2 compared to group 3. A significant positive correlation was found between bone surface and whole bone F (r²=0.94), as well as between plasma and bone surface (r²=0.71) and plasma and whole bone (r²=0.74). CONCLUSIONS: Data suggest that both bone surface and whole bone are suitable biomarkers of chronic F exposure in rats and plasma may be used as indicator of bone fluoride levels.


2009 ◽  
Vol 24 (3) ◽  
pp. 189-194 ◽  
Author(s):  
Frederico Theobaldo Ramos Rocha ◽  
Laercio Gomes Lourenço ◽  
Mário Jorge Jucá ◽  
Valéria Costa ◽  
Antenor Teixeira Leal

PURPOSE: To evaluate chemoprevention by celecoxib in cases of reflux-induced gastric adenocarcinoma, in Wistar rats that underwent gastrojejunostomy. METHODS: Sixty male Wistar rats of average age three months underwent surgery and were distributed into three groups: group 1, exploratory laparotomy; group 2, gastrojejunostomy; and group 3, gastrojejunostomy and daily celecoxib administration. After 53 weeks, the animals were sacrificed. Changes in the mucosa of the gastric body of group 1 and in the gastrojejunal anastomosis of groups 2 and 3, observed in histopathological and immunohistochemical examinations, were compared. All statistical analyses were performed using Epi-Info®, version 3.4.3. RESULTS: Comparison between groups 2 and 3 relative to the presence of adenocarcinoma showed a statistically significant difference (p=0.0023). Analysis of the association between groups 2 and 3 relative to COX-2 expression also showed a statistically significant difference (p=0.0018). CONCLUSION: Celecoxib had an inhibiting effect on gastric carcinogenesis induced by enterogastric reflux in an animal model.


2012 ◽  
Vol 27 (12) ◽  
pp. 905-911 ◽  
Author(s):  
Jairo Zacchê de Sá ◽  
José Lamartine de Andrade Aguiar ◽  
Adriana Ferreira Cruz ◽  
Alexandre Ricardo Pereira Schuler ◽  
José Ricardo Alves de Lima ◽  
...  

PURPOSE: To evaluate the effect of local nitroglycerin on the viable area of a prefabricated flap for vascular implant in rats, and to investigate the surgical delay procedure. METHODS: A femoral pedicle was implanted under the skin of the abdominal wall in forty Wistar rats. The animals were divided into four groups of ten: group 1 - without surgical delay procedure and local nitroglycerin; group 2 - with surgical delay procedure, but without local nitroglycerin; group 3 - without surgical delay procedure, but with local nitroglycerin; and group 4 - with simultaneous surgical delay procedure and local nitroglycerin. The percentages of the viable areas, in relation to the total flap, were calculated using AutoCAD R 14. RESULTS: The mean percentage value of the viable area was 8.9% in the group 1. 49.4% in the group 2; 8.4% in the group 3 and 1.1% in the group 4. There was significant difference between groups 1 and 2 (p=0.005), 1 and 4 (p=0.024), 2 and 3 (p=0.003), 2 and 4 (p=0.001). These results support the hypothesis that the closure of the arterial venous channels is responsible for the phenomenon of surgical delay procedure. CONCLUSION: Local nitroglycerin did not cause an increase in the prefabricated viable flap area by vascular implantation and decreased the viable flap area that underwent delay procedures.


1986 ◽  
Vol 14 (2) ◽  
pp. 135-139 ◽  
Author(s):  
C. L. Hastings ◽  
T. C. K. Brown ◽  
R. L. Eyres ◽  
R. C. Oppenheim

Eight mongrel puppies were studied at intervals of a few weeks. Lignocaine 4mg/kg was infused over 60 seconds. Frequent samples were taken over 30 minutes for plasma lignocaine assay. Initially the concentrations were significantly higher in the oldest group (178–191 days) but after 10 minutes the youngest group (3–16 days) had significantly higher levels than the other groups. Pharmacokinetic data derived included the rate constants k21, k12 (drug movement between two compartments), k10 (elimination from the central compartment), and the volume of distribution (Vβ). The elimination rate constant k10 was significantly lower in Group 1 (3–16 days) than all other groups and Group 2 (37–57 days) was lower than Group 4 (178–191 days). The calculated β half-life was significantly longer in the youngest group than the others. There was no significant difference in the volume of distribution between these age groups — up to 6 months.


2009 ◽  
Vol 9 (4) ◽  
pp. 290-295 ◽  
Author(s):  
Nergiz Yılmaz ◽  
Özlem Nisbet ◽  
Cevat Nisbet ◽  
Gözlem Ceylan ◽  
Fatih Hoşgör ◽  
...  

The aim of this study was to describe and quantify the therapeutic value of honey in oral mucosal ulcers healing in comparison with Glyceroloxytriester (TGO). We also aimed to biochemically evaluate the healing effects of honey which had been collected from the Blacksea region flora on mucosal ulcers resulting in material loss.Thirty wistar rats (240±30 g) were enrolled in this study. Excisional wounds were performed in all rats for animal oral mucosal ulcer model. They were randomly allocated to three groups: group 1 was treated with Apitherapeutic agent or honey (0,1 ml, 2x1), group 2 was treated with TGO (0,1ml, 2x1) locally, Group 3 served as the control group.Following the surgical procedure on day 7, biopsy specimens were taken from right buccal mucosa and on day 14 biopsy specimens were taken from left bucal mucosa in all rats. Afterwards, hydroxy pyroline levels were measured. Data were analyzed statisticallyThere was no statistically significant difference between Group 1 and 2, and also between Group 2 and 3, but there was statistically significant difference between Group 1 and 3 on day 7. There was no statistically significant difference between Group 1, 2 and 3 on day 14.


2006 ◽  
Vol 49 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Rita de Cássia da Silveira e Sá ◽  
Magda Narciso Leite ◽  
Vera Maria Peters ◽  
Martha de Oliveira Guerra ◽  
Reinaldo Nóbrega de Almeida

This work makes an assessment of the dominant lethality of Mikania glomerata in male Wistar rats. Adult male received 1 mL of M. glomerata hydroalcoholic extract at a dose level of 3.3 g/kg body weight for 52 days and were mated with untreated females for seven weeks (group 1) or one week prior to the beginning of treatment and on the week following the end of treatment (group 2). The parameters analyzed were: number of implanted embryos, resorptions and corpora lutea; mating, gestation, preimplantation loss, implantation and resorption indexes (group 1); number of offspring and weaning animals (group 2). The administration of M. glomerata did not show any impairment of fertility and no significant difference in the parameters analyzed, suggesting an absence of mutagenic effect on Wistar rats.


Author(s):  
G. Ramya Bala Prabha ◽  
M. Nagulu

The present study was aimed to conduct to evaluate any possible pharmacokinetic interactions between albuterol and timolol. Study was conducted in Male Wistar rats; animals were divided in to three groups, Group I received albuterol alone in single dose / day in healthy rats. Group 2 received timolol alone in single dose / day in healthy rats. Group 3 received albuterol and timolol concomitant administration in healthy rats as a single dose / day. The treatment was given on day one and day 8 both alone albuterol and timolol concomitantly used both the drugs. There was no significant difference in both cmax, tmax and AUC0-t and AUCo-inf of albuterol alone and combination of timolol on day 1 and day 8 respectively. Based on the results obtained from kinetic study it is evident that the single dose of albuterol and timolol individually and concomitantly treated shows no statistically significant interactions in its pharmacokinetic parameters.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4935-4935 ◽  
Author(s):  
Martin Hoffmann ◽  
Raoul Bergner ◽  
Marion Stützle ◽  
Michael J. Uppenkamp ◽  
Rabea Foerster

Abstract Abstract 4935 Background Doxorubicin (Dox) is the back bone of chemotherapy in the therapy of several types of carcinomas, lymphomas and acute leukemias. Obese patients (Body Mass Index > 30) have due to their body weight a relatively high Body Surface Area (BSA). Their calculated doxorubicin dose is therefore greater than for patients with normal weight. This could lead to overdosing in case of e.g. a reduced drug clearance. Otherwise a recent study demonstrated a worse outcome in women receiving adjuvant therapy with reduced chemotherapy dose. Patients and methods Eligible were patients above the age of 18 years and receiving the first or second cycle of a Doxorubicin-based chemotherapy. Patients were divided due to their BMI in three groups (group 1: BMI < 25; group 2: BMI ≥ 25 and < 30, group 3: BMI ≥ 30). Dox was administered in a dose of 50 mg/m2 as infusion over 15 minutes. Blood samples were obtained at 0, 0.25, 0.5, 1, 2, 3, 4, 8, 12, 24 hours. Dox and its metabolite Doxorubicinol were measured by High Performance Liquid Chromatography. Area under the curve (AUC), clearance (Cl), half life (T1/2), and volume of distribution in steady state (Vss) were calculated using a 2-compartment-model for Dox and a non-compartmental-model for Doxorubicinol with PK software (WinNonlin). Results 31 Patients with untreated indolent or aggressive lymphomas were included in the study. Patients received CHOP-21 or CHOP-14 + G-CSF. 11 were in group 1, 10 in group 2 and 10 in group 3. 18 patients were male and 13 female. The mean age was 66 ± 10 years. The mean BMI was 27.9 ± 4.9 (group 1: 22.5 ± 2.1 group 2: 28.0 ± 1.4; group 3: 33.9 ± 1.8). Patients received a mean dose of 95.5 mg Dox (87.3 ± 8.1, 99.1 ± 10.2, 100.8 ± 7.5). We found a significant difference between the groups for the AUC by an analysis of variance. (p=0.014). This was also noticed for the differences between group 1 and 3 (p=0.029) and 2 and 3 (0.042) evaluated by a Scheffe test. The Cl showed no statistically significant difference (p=0.079). The BMI correlated (P=0.046) with the AUC. The AUC of Doxorubicinol was significantly different between the three groups (p=0.009), as was the clearance (p=0.04). The BMI was correlated with the AUC (p=0.009), the Cl (p=0.003), and T1/2 (p=0.036). We did not find any correlation between the pharmacokinetic parameters of Dox or Doxorubicinol and response to therapy. The evaluation of the hematological toxicity showed a non significant trend for higher WHO grade 3–4 leucopenia in patients with increased AUC of Dox. Conclusion The AUC in the patient group with BMI ≥ 30 was increased. This was caused by a reduced clearance as there was no relevant difference to the other groups in Vss. This suggested that Dox and Doxorubicinol penetrate only minimally into the fat tissue. However, the pharmacokinetic parameters of Dox and Doxorubicinol in non obese and obese patients showed considerable interindividual variability. The hematologic toxicity in obese patients was not significantly increased and therapy outcome did not correlate with any pharmacokinetic parameter. Thus, based on these data, we can not recommend a reduction of dose for Dox in patients up to a BMI of 35. Disclosures: No relevant conflicts of interest to declare.


VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


2021 ◽  
Vol 28 (3) ◽  
pp. 328-338
Author(s):  
Ogbutor Udoji Godsday ◽  
Nwangwa Eze Kingsley ◽  
Nwogueze Bartholomew Chukwuebuka ◽  
Chukwuemeka Ephraim ◽  
Ezunu Emmanuel ◽  
...  

Decline in normal physiological pulmonary function has been attributed to premorbid conditions such as prehypertension. Research evidence suggests that physical activity reduces age-related decline in pulmonary function and improves the efficiency of the lungs in prehypertensive patients. However, there is a scarcity of data evidence relating to isometric exercise and pulmonary function. Furthermore, the interrelationship between the intensity and duration of isometric exercise and pulmonary function in these patients is still uncertain. Therefore, this study was undertaken to investigate the effect of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. To determine the effectiveness of isometric handgrip exercise on pulmonary function capacity in adults with prehypertension. A quasi experiment using a pre- and post-exercise method was carried out in two out-patients hospital settings. The sample comprised 192 sedentary pre-hypertensive subjects, aged between 30–50 years, that were randomly distributed into three groups of 64 participants each. The subjects performed, for 24 consecutive days, an isometric handgrip exercise at 30% Maximum Voluntary Contraction (M.V.C.). At the end of the 24 days, group one (GP1) discontinued, while group two (GP2) continued the exercise protocol for another 24 consecutive days and group three (GP3) continued with the exercise protocol for another 24 consecutive days but at 50% M.V.C. Determinants of lung function (outcomes) were Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), FEV1/FVC Ratio and Peak Expiratory Flow Rate (PEFR). The study shows that there was no statistically significant difference in the pre- and post-exercise outcomes for FEV1, FVC, FEV1/FVC Ratio and PEFR after 24 days for group 1. In group 2, there was a statistically significant difference in the FVC [(mean = 0.12 ± 0.12), (p = 0.002)], FEV1 [(mean = 0.15 ± 0.17), (p = 0.003)] and PEF [(mean = 0.85 ± 0.35), (p = 0.001)] after 48 days. In group 3, there was a statistically significant difference (p = 0.001) in all the outcomes assessed after 48 days. There was a between groups difference in favour of group 2 compared with group 1 for outcomes of FEV1 [(mean = 0.142 ± 0.68), (p = 0.005)] and PEF [(mean = 0.83 ± 0.19), (p = 0.0031)]. There was statistically significant difference in favour of group 3 compared to group 2, by increasing the exercise intensity from 30% to 50% M.V.C., for outcomes of FVC [mean change = 0.10 ± 0.052), (p = 0.005)], FEV1/FVC [mean change = 3.18 ± 0.75), (p = 0.017)] and PEF [(mean change = 0.86 ± 0.35), (p = 0.001)] after 48 days. Isometric handgrip exercise (after 48 days at 30% to 50% M.V.C.) improves outcomes of pulmonary function capacity in adults with prehypertension. Meanwhile, duration and/or increase in intensity of the isometric effort significantly contributed to the affects attained.


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