Altered pharmacokinetics and pharmacodynamics of repaglinide by ritonavir in rats with healthy, diabetic and impaired hepatic function

2016 ◽  
Vol 31 (2) ◽  
Author(s):  
Thirumaleswara Goud ◽  
Srinivas Maddi ◽  
Devanna Nayakanti ◽  
Rajendra Prasad Thatipamula
Keyword(s):  
Cytochrome P450 ◽  
Plasma Concentration ◽  
Organic Anion ◽  
Hepatic Function ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Impaired Hepatic Function ◽  
Significant Difference

AbstractRitonavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450 3A4. To treat diabetes mellitus in HIV, repaglinide is coadministered with ritonavir in the clinic. Multiple cytochrome P450 (CYP) isoforms are involved in the metabolism of repaglinide like CYP2C8 and CYP 3A4. In order to predict and understand drug-drug interactions of these two drugs, the pharmacokinetics and pharmacodynamics (PK/PD) of repaglinide and ritonavir were studied in normal, diabetic and hepatic impaired rats. The purpose of the study was to assess the influence of ritonavir on the PK/PD of repaglinide in rats with normal, diabetic and impaired hepatic function.Human oral therapeutic doses of ritonavir and repaglinide were extrapolated to rats based on the body surface area. Ritonavir (20 mg/kg, p.o.), alone and along with repaglinide (0.5 mg/kg, p.o.), was given to normal, diabetic and hepatic impaired rats, and the PK/PD were studied.The pharmacokinetic parameters like peak plasma concentration (Cmax), area under the plasma concentration time profile (AUC) and elimination half life of repaglinide were significantly (p<0.0001) increased when compared to repaglinide control rats. The repaglinide clearance (CL) was significantly (p<0.0001) decreased in the presence of ritonavir treatment. In the presence of ritonavir, repaglinide hypoglycemic activity was increased significantly (p<0.0005) when compared with repaglinide control group.The significant difference in the PK/PD changes have been due to the increased plasma exposure and decreased total body clearance of repaglinide, which may be due to the inhibition of the CYP P450 metabolic system and organic anion-transporting polypeptide transporter by ritonavir.

scholarly journals Evaluation of pharmacokinetic and pharmacodynamic interaction between repaglinide and atazanavir in healthy, diabetic and hepatic impaired rats: possible inhibition of CYP3A, OATP, and P-glycoprotein transporters

ADMET & DMPK ◽  
2016 ◽  
Vol 4 (3) ◽  
pp. 269 ◽  
Author(s):  
Thirumal Eswara Goud ◽  
Srinivas Maddi ◽  
Nayakanti Devanna ◽  
Thatipamula Rajendra Prasad
Keyword(s):  
Metabolic Syndrome ◽  
Blood Glucose ◽  
Plasma Concentration ◽  
Peak Plasma ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
The Metabolic Syndrome ◽  
Significant Difference ◽  
Blood Glucose Concentrations

<p>The metabolic syndrome in HIV infected patients is particularly associated with the use protease inhibitors. Atazanavir is an inhibitor of the cytochrome P 450 (CYP) system, in particular CYP3A4 and CYP2C9 which can affect the metabolism of several drugs. To treat metabolic syndrome in HIV patients repaglinide is used and it is a short acting insulin secretagogues undergoing metabolism with CYP 3A4 and CYP 2C8 enzyme system. The purpose of this study was to assess the possible pharmacokinetic and pharmacodynamic drug interaction of repaglinide and atazanavir in healthy, diabetic and impaired hepatic function rats. Human oral therapeutic doses of atazanavir and repaglinide were extrapolated to rats based on the body surface area. The pharmacokinetic parameters and blood glucose concentrations of repaglinide were determined after oral administration of repaglinide alone (0.5 mg/kg) and in the presence of atazanavir (36 mg/kg) in normal, diabetic and hepatic impaired rats. The pharmacokinetics (PK) and blood glucose concentrations of repaglinide were significantly altered in the presence of atazanavir. The peak plasma concentration (C<sub>max</sub>), area under the plasma concentration time profile (AUC) and elimination half-life of repaglinide were significantly (P&lt;0.0001) increased. The repaglinide clearance (CL) was significantly (P&lt;0.0001) decreased in the presence of atazanavir treatment. In the presence of atazanavir, repaglinide hypoglycaemic activity was increased significantly (P&lt;0.0001) when compared with the repaglinide control group. The present study demonstrated the significant difference in the PK/PD changes due to the enhanced bioavailability and decreased total body clearance of repaglinide may be due to the inhibition of the CYP P450 metabolic system, OATP and P-gp transporters by atazanavir.</p>

scholarly journals The Effects of Acute Hydrogen Sulfide Poisoning on Cytochrome P450 Isoforms Activity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Xianqin Wang ◽  
Mengchun Chen ◽  
Xinxin Chen ◽  
Jianshe Ma ◽  
Congcong Wen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Hydrogen Sulfide ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Upper Respiratory Tract ◽  
Significant Difference ◽  
Cytochrome P450 Isoforms ◽  
Upper Respiratory ◽  
And Control

Hydrogen sulfide (H2S) is the second leading cause of toxin related death (after carbon monoxide) in the workplace. H2S is absorbed by the upper respiratory tract mucosa, and it causes histotoxic hypoxemia and respiratory depression. Cocktail method was used to evaluate the influences of acute H2S poisoning on the activities of cytochrome P450 isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19, and CYP2C9, which were reflected by the changes of pharmacokinetic parameters of six specific probe drugs, bupropion, metoprolol, midazolam, phenacetin, omeprazole, and tolbutamide, respectively. The experimental rats were randomly divided into two groups, control group and acute H2S poisoning group (inhaling 300 ppm for 2 h). The mixture of six probes was given to rats by oral administration and the blood samples were obtained at a series of time points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by LC-MS. The results for acute H2S poisoning and control groups were as follows: there was a statistically significant difference in the AUC andCmaxfor bupropion, metoprolol, phenacetin, and tolbutamide, while there was no statistical pharmacokinetic difference for midazolam and omeprazole. Acute H2S poisoning could inhibit the activity of CYP2B6, CYP2D6, CYP1A2, and CYP2C9 in rats.

Effectiveness Of Toilet Training Education On Mother's Behavior And Toddler Age Toilet Training Ability (18-36 Months)

2020 ◽  
Vol 5 (2) ◽  
pp. 49-55
Author(s):  
Hafiko Andresni ◽  
Zahtamal Zahtamal ◽  
Winda Septiani ◽  
Mitra Mitra ◽  
Lita Lita
Keyword(s):  
Sampling Technique ◽  
T Test ◽  
The Body ◽  
Toilet Training ◽  
Wilcoxon Test ◽  
Control Group ◽  
Maternal Knowledge ◽  
Control Group Design ◽  
Significant Difference

ABSTRACT Toilet training is an effort to train children to be able to control and urinate (BAK) and defecate (BAB). Toilet training is one of the main tasks of children at toddler age. Toilet training is one of the main tasks of children in toddler age which is very important to be done to create independence in children in controlling BAK and BAB and children know the parts of the body and their functions. Data in 2012 shows that ± 60% of parents do not teach toilet training to children from an early age. The aim of the study was to find out the effectiveness of toilet training education on maternal behavior and toilet skills in toddler age training (18-36 months). The study was conducted in July-August 2018. This type of quantitative research used the design of the Quasy pretest and posttest experiment with non-equivalent control group design. Samples were 36 mothers and 36 children with purposive sampling technique. Data analysis used Paired t test, Wilcoxon test, Man-Whitney test an Independent t test. The results showed that toilet training education through lecture methods, modules and maze games was more effective than toilet training education through lecture and leaflet methods on children's knowledge and abilities. Conversely, for the role of mothers in supervision there is no significant difference in effectiveness. Health education is recommended in health promotion programs to increase maternal knowledge, the role of mothers and the ability of toilet training children independently. Keywords: Toilet training, Lecture method, Module, Maze game, Leaflet, Knowledge, Role of mother, Children's ability.

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

A study on the safety evaluation of buphrenorphine administered through an autoinjector compared with manual injection using haematological and biochemical variables in rats

2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar
Keyword(s):  
Body Weight ◽  
Research Work ◽  
Safety Evaluation ◽  
Weight Ratio ◽  
The Body ◽  
Control Group ◽  
Body Weight Ratio ◽  
Significant Difference ◽  
Manual Group ◽  
Significant Change

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.

Congenital Heart Disease and Childhood Adjustment

1971 ◽  
Vol 2 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Edward T. Auer ◽  
Audrey G. Senturia ◽  
Moisy Shopper ◽  
Ralph L. Biddy
Keyword(s):  
Body Image ◽  
Surgical Intervention ◽  
Intellectual Functioning ◽  
Emotional Disturbances ◽  
The Body ◽  
Psychiatric Clinic ◽  
Control Group ◽  
Significant Difference ◽  
Figure Drawings ◽  
Childhood Adjustment

This report deals with the findings from a study of twenty-eight children, all of whom had ventricular septal defects and were studied by the same cardiovascular team. One-half of the group had a surgical procedure for correction of the defect. The study investigated three problems in children with ventricular septal defect ( VSD). (1) Do children with surgical intervention for VSD show greater impairment of intellectual functioning than non-operated children? (2) Do children with surgical intervention show greater emotional disturbance than non-operated children? (3) Do children with surgical intervention show greater alteration of body image than do non-operated children? Data were collected using questionnaires, family interviews, subject interviews, medical records, school reports, physicians' reports and Human Figure Drawings, both inside and outside the body. The findings conclude that ( a) operated children do demonstrate significantly more impairment of intellectual functioning; ( b) there was no significant difference in the incidence of emotional disturbances between the two groups but that these twenty-eight children with VSD were more similar emotionally to children in a psychiatric clinic group than in a control group; and ( c) the only indication of altered body image was found in the greater frequency with which bones were drawn by the operated group.

scholarly journals Optimalisasi Pertumbuhan Bayi dengan Baby Massage and Spa

2019 ◽  
Vol 10 (2) ◽  
pp. 276
Author(s):  
Yusari Asih ◽  
I Gusti Ayu Mirah WS
Keyword(s):  
Body Length ◽  
Head Circumference ◽  
Intervention Group ◽  
Sampling Technique ◽  
Holistic Approach ◽  
The Body ◽  
Control Group ◽  
P Value ◽  
Control Group Design ◽  
Significant Difference

<p><span>Baby Massage and Spa was a traditional effort that uses a holistic approach through comprehensive care using a combination of massage and water therapy methods that are carried out in an integrated manner to balance the body, mind, and feelings. Age 3-6 months is the right time for babies to do massage and spa. The purpose of this study was to determine the effect of baby massage and spa on the growth of infants aged 3-5 months in Pringsewu District in 2018. This study uses a quasi-experimental approach with research design pre and post-test with control group design. The purposive sampling technique was taken with a sample of 30 infants as the intervention group and 30 infants as the control group. Data were processed using computerization and analyzed using the T-Test. The results showed that there were significant differences between body weight, body length and baby head circumference in the pre and post-treatment. There was no significant difference in the average increase in infant weight between babies who were carried out by baby massage and spa with babies who were not carried out by baby massage and spa with p-value 0.116. There is a significant difference in the baby's body length and head circumference performed by baby massage and spa with those not carried out by baby massage and spa with p-value 0.000. Baby Massage and Spa has a significant effect on increasing the growth of babies aged 3-5 months.</span></p><p><span> </span></p>

scholarly journals A randomised, open label comparative study of hydroxychloroquine with betamethasone oral mini pulse in the management of patients with alopecia areata

2021 ◽  
Vol 10 (2) ◽  
pp. 187
Author(s):  
Jeyasudha Jambusayee ◽  
Kulur Mukhyaprana Sudha
Keyword(s):  
Alopecia Areata ◽  
Life Quality ◽  
Autoimmune Disorder ◽  
Study Groups ◽  
Pulse Therapy ◽  
The Body ◽  
Control Group ◽  
Study Group ◽  
Open Label ◽  
Significant Difference

Background: Alopecia areata is an autoimmune disorder causing patchy hair loss on scalp and other parts of the body and leading to poor self-esteem and anxiety in patients. Treatment with topical or systemic drugs like steroids or other immunosuppressants is associated with adverse effects. Hydroxychloroquine is an antimalarial drug, with T cell modulating function. This study was undertaken to assess the safety, efficacy and tolerability of Hydroxychloroquine in Alopecia areata compared to betamethasone oral mini pulse (OMP) therapy. Methods: 60 patients with alopecia areata were randomized into two groups of 30 each. Control group received tab. betamethasone 5 mg/day on two consecutive days of week for 12 weeks and Study group received tab. hydroxychloroquine 200 mg/day for 12 weeks. They were followed-up for further 12 weeks. Scale of alopecia tool, dermatology life quality index and global assessment at baseline, 12 weeks and 24 weeks were used to assess the outcome.Results: 94 patients were screened and 60 patients were included. All patients completed the study. At the end of 12 weeks, there was a statistically significant reduction in SALT and DLQI scores in both control and study groups. But at the end of 24 weeks, the study group showed an increase in the scores. Relapses were more in the study group. No significant difference in the incidence of adverse events was noted between the two groups.Conclusions: Hydroxychloroquine 200 mg/day is less efficacious in the management of alopecia areata in comparison to betamethasone oral mini pulse therapy.

scholarly journals Perbedaan Kadar Glutation (GSH) Hepar Tikus Putih Jantan (Rattus norvegicus) yang diinduksi Parasetamol Dosis Toksik dengan Pemberian Ekstrak Daun Kelor (Moringa oleifera)

2020 ◽  
Vol 20 (1) ◽  
pp. 247
Author(s):  
Nur Insani ◽  
H.M.T Kamaluddin ◽  
Swanny Swanny
Keyword(s):  
Oxidative Stress ◽  
Treatment Group ◽  
Leaf Extract ◽  
The Body ◽  
Control Group ◽  
Bb Rat ◽  
Toxic Dose ◽  
Experimental Animals ◽  
Significant Difference ◽  
Group Ii

Glutathione (GSH) transferase deficiency due to paracetamol exposure causes further oxidative stress to liver necrosis. To reduce oxidative stress that can cause damage to the liver of the body requires antioxidants. One plant to treat liver disease is the kelor leaf (because it has an active flavonoid material also has antioxidant activity). This study was conducted to determine the difference of glutathione hepar levels of male white rat induced paracetamol toxic dose by giving kelor leaf extract. The type of research is experimental laboratory in vivo with rancagan randomized post test only control group design. With the stages as follows 1.Leaf Extract Kelor with Ethanol 96%, 2.Perpeteration of experimental animals, 3.Treatment of experimental animals by giving extract of 3-dose of kelor leaf that is KP I 250 mg / 200 gr BB rat, KP II 500 mg / 200 gr BB rat, KP III 1000 mg / 200 gr BB rat  for 14 days combined with paracetamol dose 2 gr / 200 gr BB rat compared with the negative control group (group given only paracetamol dose 2 gr / 200 gr BB rat) and control group positif only fed regular feed for 14 days). The result showed that there was a significant difference mean of GSH levels between all treatment groups obtained p = 0,000 (p <α) p values smaller than 0.05. There was the highest increase of GSH in treatment group II (142,7525 μmol / mg) and lowest dose of GSH in positive control group (57,1812 μmol / mg), dose paracetamol toxic dosage and kelor leaf extract 500 mg / gr BB rat can increase GSH hepar p = 0,000 (p <α) p less than 0 , 05. The conclusion of the test results showed that giving of kelor leaf extract at dose of treatment group II can increase GSH hepar level significantly

scholarly journals The effect of ethanol extract of pegagan (Centella asiatica) on the performance of Wistar rats after restraint stress

2010 ◽  
Vol 8 (1) ◽  
pp. 11-16
Author(s):  
BAARID LUQMAN HAMIDI ◽  
SAMIGUN SAMIGUN ◽  
ANIK LESTARI
Keyword(s):  
Restraint Stress ◽  
Wistar Rats ◽  
Radial Maze ◽  
Centella Asiatica ◽  
Ethanol Extract ◽  
The Body ◽  
Control Group ◽  
Error Type ◽  
Stress Group ◽  
Significant Difference

Hamidi BL, Samigun, Lestari A. 2010. The effect of extract ethanol of pegagan (Centella asiatica) on the performance of Wistar rats after restraint stress. Biofarmasi 8: 11-16. The aim of this research was to investigate the effects of extract ethanol of pegagan (Centella asiatica) after treated with restraint stress by measuring the eight arms radial maze performance of rats. Pre-test and post-test controlled groups design was applied in this research. Male Wistar rats (Rattus novergicus) with the mean age of 8 weeks and the body weight of 150-200 grams which used for sample were divided randomly into 4 groups, each group consisted of 6 rats, i.e. (i) control group (without any treatment), (ii) stress group (it was given by restraint stress for 2 hours/day for each rat), (iii) pegagan group (it was given by 0.3 mg/g BW/day/rat extract ethanol of pegagan), and (iv) pegagan and stress group (it was given by 0.3 mg/g BW/day/rat extract ethanol of pegagan and restraint stress for 2 hours/day for each rat). The treatments were given for 21 days. Within 12 days for each pre-treatment and post-treatment, a test on the eight arm radial maze was conducted on individual rat to observe its performance. The assessment of rat performance in the eight arms radial maze test was conducted based on error type B. Kruskal-Wallis and Mann-Whitney tests with SPSS for Windows 16 version were applied to analyze statistically the difference between four groups. Kruskal-Wallis test was used to show the significant performance level difference between four groups of rats with p=0.001, while Mann-Whitney test was used to determine the significant difference between stress group and pegagan group (p=0.001), also stress group and pegagan and stress group (p=0.001). The result of research showed that there was no significant difference between control group and stress group (p=0.051), control group and pegagan group (p=0.143), control group and pegagan and stress group (p=0.143), also pegagan group and pegagan and stress group (p=0.952). It was concluded that extract ethanol of pegagan improved the performances of rats on the eight arms radial maze after treated with restraint stress.

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