scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PENTOXIFYLLINE USING NATURAL MUCOADHESIVE POLYMERS

2019 ◽  
pp. 153-157
Author(s):  
GNANASEKARAN JOHN SELVARAJ ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Drug Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Fold Increase ◽  
Ocimum Basilicum ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Time Curve ◽  
Significant Difference

Objective: The present study was aimed to alter the pharmacokinetic parameters of the drug pentoxifylline using a novel natural mucoadhesive polymer from two different plants, Manilkara zapotta Linn and Ocimum basilicum Linn. Methods: The polymer was isolated and six batches of mucoadhesive tablets of pentoxifylline was formulated with 3 different concentrations of each polymer. The best formulation from each of the polymer was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as such as Cmax, tmax, AUC, AUMC, λz, t1/2, and MRT were determined. Results: The plasma drug concentration vs time curve shows the extended-release of pentoxifylline when compared with the conventional marketed formulation. The results show that there is no change in the peak plasma concentration, but the significant difference was observed in t½, which showed approximately 2.5 fold increase from 2.44 to 6.87 h and the AUC showed five-fold increase from 22.40 to 117.19 μg*h/ml, and other pharmacokinetic parameters, when compared with the marketed formulation. Conclusion: The isolated polymer from the plants Manilkara zapotta Linn. and Ocimum basilicum Linn can be used as a carrier for developing mucoadhesive formulations and it alter the pharmacokinetic of pentoxifylline positively.

scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PROTON PUMP INHIBITORS USING TRANSDERMAL DRUG DELIVERY SYSTEM

2021 ◽  
pp. 371-375
Author(s):  
M. R. SHIVALINGAM ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Plasma Concentration ◽  
Residence Time ◽  
Proton Pump ◽  
Drug Concentration ◽  
Mean Residence Time ◽  
Fold Increase ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Transdermal Patches

Objective: The present study was aimed to find out the effect of transdermal patches of proton pump inhibitors pantoprazole and esomeprazole on the alteration of pharmacokinetic parameters of these drugs. Methods: The transdermal patches were formulated by the solvent evaporation technique using polymers HPMC E5 with PVP K 30 and HPMC E5 with Eudragit L100 in different ratios. The best formulation from each of the drug pantoprazole and esomeprazole was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under the curve (AUC), area under first moment curve (AUMC), elimination rate constant (λz), biological half-life (t1/2), and mean residence time (MRT) were determined. Results: The plasma drug concentration vs time curve shows the extended-release of the drugs pantoprazole and esomeprazole when compared with the marketed formulation. The results show that there is no change in the peak plasma concentration, but a significant difference was observed in all the pharmacokinetic parameters. The AUC showed 6 fold increase for pantoprazole from 8.91 to 55.20 μg*h/ml and 3.5 fold increase for the drug esomeprazole from 7.86 to 28.53 μg*h/ml, and the mean residence time also showed 2 fold increase for the transdermal patches when compared with the marketed formulations. Conclusion: The increase in tmax, AUC, and MRT values of the formulated transdermal patches with the values of the marketed formulation of both the drugs, revealed that the transdermal patches can be used to deliver the drug for an extended period and also can alter the pharmacokinetics of pantoprazole and esomeprazole.

Prediction of Plasma Drug Concentration Profiles and Pharmacokinetic Parameters of Nifedipine Commercial Tablets using the Convolution Method

2021 ◽  
pp. 5380-5384
Author(s):  
Hamzah Maswadeh ◽  
Ahmed A. H. Abdellatif ◽  
A. Amin Mohammed ◽  
Aiman Y. Alwadi ◽  
A. Ibrahim Mohamed
Keyword(s):  
Drug Concentration ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Concentration Profiles ◽  
Plasma Drug ◽  
First Order ◽  
Convolution Method

The aim of this study was to predict the blood/plasma drug concentration profiles for five brand of nifedipine present on the Saudi Arabia market by using the numerical convolution method and to estimate the pharmacokinetic parameters (Cmax, Tmax, Ka, K and Vd) by the application of the residual method to the predicted plasma drug concentration profiles. Results showed that the higher Cmax was 118.95ng/ml for brand A2 and the lower Cmax was 72.29ng/ml for brand A3. The Tmax was ranged from 2.3 hr to 4.9 hr for brands A2 and A3 respectively. The total area under plasma drug concentration curve (AUCinf.) was in lower value equal to 585.59 ng x hr/ml for brand A2 and the higher value was for brand A5 equal to 743.52ng x hr/ml. The volume of distribution was also increased from 52.5 L for free nifidipine to 72 L for brand A1. The predicted first order elimination rate constant was decreased from 0.34 hr-1 for free nifedipine to 0.17 hr-1 for brand A3. The half-life of nifedapine was increased from 2 hours for free drug to 3.93 hours for brand A3. From this study it can be concluded that brands present in the market that shows similarity in accordance to the Dissimilarity factor f1 are not always guaranty that they will be bioequivalent in vivo and vice versa. Also, this study indicates that the method of convolution is a useful tool for prediction of bioequivalence of different brands present on the market.

scholarly journals NANO-SPONGE NOVEL DRUG DELIVERY SYSTEM AS CARRIER OF ANTI-HYPERTENSIVE DRUG

2019 ◽  
pp. 47-63
Author(s):  
MONA IBRAHIM EL-ASSAL
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Concentration ◽  
Entrapment Efficiency ◽  
Plasma Drug Concentration ◽  
Production Yield ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug

Objective: The study was designed to prepare Nano-sponge formulation loaded with nifedipine. Studying parameters which affecting the formulas in addition to pharmacokinetics and toxicity tests. Methods: Nine Nano-sponge formulations were prepared by the solvent evaporation technique. Different ratios of polymer ethylcellulose, CO-polymers β-cyclodextrin and hydroxypropyl β-cyclodextrin in addition to solubilizing agent polyvinyl alcohol were used. Thermal analysis, X-ray powder diffraction (XRPD), shape and surface morphology, particle size, %production yield, %porosity, % swelling, and % drug entrapment efficiency of Nano-sponge were examined. Release kinetic also studied beside comparison of pharmacokinetic parameters of the optimum choice formula and marketed one in addition to Toxicological consideration. Results: Particle size in the range of 119.1 nm to 529 nm which were increased due to the increase in the concentration of polymer to the drug. Nano-sponge revealed porous, spherical nature. Increased in the drug/polymer molar ratios (1:1 to 1:3) may increase their % production yield ranged from 62.1% to 92.4%. The drug content of different formulations was in the range of 77.9% to 94.7%, and entrapment efficiency was in the range of 82.72 % to 96.63%. Drug released in controlled sustained pattern and followed Higuchi, s diffusion mechanism. Pharmacokinetic parameters of optimized formula showed significant higher maximum plasma drug concentration, area under plasma concentration-time curve, volume of distribution and mean residence time. Nano-sponge loaded drug proved biological safety at low concentrations. Conclusion: Nano-sponge drug delivery system has showed small Nano size, porous with controlled drug release and significant-high plasma drug concentration that improved solubility, drug bioavailability and proved safety.

scholarly journals Effect of lopinavir and efavirenz on pharmacokinetics and pharmacodynamics of glibenclamide in diabetic rats

2017 ◽  
Vol 4 (6) ◽  
pp. 245
Author(s):  
Prashanth Vennapanja ◽  
Ajmera Ramarao
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Severe Hypoglycemia ◽  
Diabetic Rats ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Elimination Half ◽  
Antiretroviral Drug ◽  
The Impact

Objective: The aim of the study is whether the impact of Efavirenz and Lopinavir will increase the plasma level of Glibenclamide or not. Efavirenz and Lopinavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450-3A4. Multiple CYP isoforms are involved in the metabolism of Glibenclamide like CYP2C8 and CYP3A4. Hence there is more possibility of Efavirenz and Lopinavir to inhibit the metabolism of Glibenclamide by inhibiting CYP 3A4.Methods: Efavirenz and Lopinavir (10 mg/kg,p.o.) alone and along with Glibenclamide (10 mg/kg, p.o.) was given to normal and diabetic rats. PK/PD parameters were studied. In the rats co-treated with Efavirenz and Lopinavir and Glibenclamide.Results: The pharmacokinetic parameters like clearance of Glibenclamide was reduced, peak plasma concentration, area under the plasma concentration time curve and elimination half-life were significantly increased when compared to pioglitazone treated rats.Conclusions: This study revealed that lopinavir and efavirenz affected the disposition of Glibenclamide in rats probably by the inhibition of CYP3A4, leading to increasing Glibenclamide concentrations that could increase the efficacy of Glibenclamide or it may causes severe hypoglycemia. Therefore, its warrants to use relatively less dose of Glibenclamide than the normal dose.

scholarly journals PHARMACOKINETIC DRUG INTERACTION BETWEEN CLOPIDOGREL AND ESOMEPRAZOLE IN ADULT HEALTHY MALE VOLUNTEERS

2017 ◽  
Vol 10 (7) ◽  
pp. 336
Author(s):  
Bhargav K ◽  
Venkata Subbareddy B ◽  
Venkata Sivakrishna K ◽  
Himaja G ◽  
Samuel Gideon Georgep ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Antiplatelet Agent ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
Poor Responders ◽  
Healthy Male ◽  
Indwelling Catheter ◽  
Significant Difference

Objective: Proton pump inhibitors (PPIs) are known to impair cytochrome P2C19 mediated activation of clopidogrel, the antiplatelet agent used for cardiovascular risk prevention. Esomeprazole is an optical isomer of omeprazole with better efficacy and tolerability than conventional PPIs. Esomeprazole is often co-administered with clopidogrel considering the risk of associated gastrointestinal bleeding. This study was designed to determine the effect of esomeprazole on the mean pharmacokinetic profile clopidogrel.Methods: A total of 14 adult healthy male participants who volunteered participation were enrolled, randomized equally into two cross-over sequences, dosed with clopidogrel and clopidogrel + esomeprazole in respective periods. Blood samples were collected through antecubital or forearm vein indwelling catheter. Concentration of clopidogrel parent prodrug in isolated plasma was determined using validated sensitive liquid chromatography – mass spectrometry. Pharmacokinetic modeling was carried out using PKSOLVER add-in for Microsoft Excel.Results: The pharmacokinetic profile of clopidogrel was non-significantly altered by esomeprazole. Statistically significant difference in peak plasma concentration, apparent volume of distribution, and clearance of clopidogrel was observed only during period II in participants co-dosed with esomeprazole (p=0.0483, 0.0011, and 0.0015, respectively). All other primary and secondary pharmacokinetic parameters displayed minor alterations during either period (p>0.05).Conclusion: The non-significant alteration of clopidogrel pharmacokinetics by esomeprazole can be potentiated by underlying predisposing factors such as the presence of CYP2C19 allelic variants and increasing the risk of cardiovascular events. Hence, co-administration of clopidogrel and esomeprazole should be under clinical monitoring and is not recommended in poor responders of antiplatelet therapy with clopidogrel.

Pharmacokinetics of Moxifloxacin in A 5/6th Nephrectomized Rat Model

1970 ◽  
Vol 2 (4) ◽  
pp. 748-755
Author(s):  
Hariprasath Kothandam ◽  
Venkatesh Palaniyappan ◽  
Sudheer Babu Idpuganti ◽  
Umamaheswari Muthusamy
Keyword(s):  
Renal Failure ◽  
Rat Model ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Area Under The Curve ◽  
Laboratory Animals ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Significant Difference ◽  
And Control

Moxifloxacin (MFLX) is a new 8-methoxyfluoroquinolone derivative with a broad spectrum of antibacterial activity. MFLX at doses of 200 and 400 mg was selected to conduct the pharmacokinetic study and the drug was given orally to control and nephrectomized rats. A 5/6th nephrectomized rat model was used in this study. The drug levels in the plasma were determined using a spectrofluorimetric assay. The pharmacokinetic parameters viz. peak plasma concentration (Cmax) and area under the curve (AUC0-8) of the nephrectomized and control rats were compared. The Cmax for both 200 and 400 mg dose of MFLX in nephrectomized rats showed significant difference(P<0.001) from the control group, which reveals the changes in the Cmax of MFLX in renal failure. The AUC0-8 for both 200 and 400 mg dose of MFLX in nephrectomized rats differ significantly (P<0.001) from sham operated control group, which implies the variation in MFLX availability in altered renal function. The AUC0-8 for 400 mg dose of MFLX in nephrectomized rats differ significantly from 200 mg dose of MFLX in nephrectomized group, which reveals that in higher dose, MFLX shows an abrupt increase in the drug availability in renal failure. It is conclude that preclinical drug monitoring of moxifloxacin in laboratory animals can be performed by using 5/6th nephrectomized rat models for determining the dose of MFLX for kidney failured patients. Various pharmacokinetic parameters determined differed in nephrectomised rats when compared to the control.

scholarly journals Comparative study of pharmacokinetics of two new fluoroquinolones, balofloxacin and grepafloxacin, in elderly subjects.

1996 ◽  
Vol 40 (12) ◽  
pp. 2824-2828 ◽  
Author(s):  
O Kozawa ◽  
T Uematsu ◽  
H Matsuno ◽  
M Niwa ◽  
S Nagashima ◽  
...  
Keyword(s):  
Drug Concentration ◽  
The Elderly ◽  
Plasma Drug Concentration ◽  
Elderly Subjects ◽  
Maximum Plasma ◽  
Plasma Drug ◽  
Urinary Recovery ◽  
Time Curve ◽  
Younger Adults ◽  
Healthy Elderly

Comparative pharmacokinetics and tolerability were studied in healthy elderly volunteers for two new fluoroquinolones, balofloxacin (Q-35) and grepafloxacin (OPC-17116), the main excretion routes being the renal and hepatic routes, respectively. Both agents were well tolerated in elderly subjects. In comparison with previously reported data from healthy younger adults, the absorption of balofloxacin was slightly delayed and urinary excretion was delayed and diminished. As a significant linear correlation was observed between renal clearance of balofloxacin and creatinine clearance, the delayed and diminished urinary recovery was attributed to the reduced renal function of the elderly subjects enrolled in the study. The absorption of grepafloxacin was also delayed, and the maximum plasma drug concentration and area under the plasma drug concentration-time curve were increased in the elderly by 31 and 48%, respectively, over those in younger adults on the basis of dose normalized to body weight. The plasma terminal elimination half-life and urinary recovery remained unchanged. Decreases in distribution volume and total body clearance in the elderly were considered to be the primary factors contributing to these differences.

scholarly journals Preparation and Pharmacokinetic Study of Daidzein Long-Circulating Liposomes

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Qiao Wang ◽  
Wenjin Liu ◽  
Junjun Wang ◽  
Hong Liu ◽  
Yong Chen
Keyword(s):  
Single Dose ◽  
Drug Concentration ◽  
Drug Loading ◽  
Plasma Drug Concentration ◽  
The Body ◽  
Molar Ratio ◽  
Terminal Phase ◽  
Plasma Drug ◽  
Ultrasonic Time ◽  
Time Required

Abstract In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions by the orthogonal design was as follows: 55 to 40 for the molar ratio of soybean phosphatidylcholine (SPC) to cholesterol, 1 to 10 for the mass ratio of daidzein to total lipid (SPC and cholesterol) (w:w), the indicated concentration of 5% DSPE-mPEG2000 (w:w), 50 °C for the hydration temperature, and 24 min for the ultrasonic time. Under these conditions, the encapsulation efficiency and drug loading of DLCL were 85.3 ± 3.6% and 8.2 ± 1.4%, respectively. The complete release times of DLCL in the medium of pH 1.2 and pH 6.9 increased by four- and twofold of that of free drugs, respectively. After rats were orally administered, a single dose of daidzein (30 mg/kg) and DLCL (containing equal dose of daidzein), respectively, and the MRT0−t (mean residence time, which is the time required for the elimination of 63.2% of drug in the body), t1/2 (the elimination half-life, which is the time required to halve the plasma drug concentration of the terminal phase), and AUC0−t (the area under the plasma drug concentration-time curve, which represents the total absorption after a single dose and reflects the drug absorption degree) of daidzein in DLCL group, increased by 1.6-, 1.8- and 2.5-fold as compared with those in the free group daidzein. Our results indicated that DLCL could not only reduce the first-pass effect of daidzein to promote its oral absorption, but also prolong its mean resident time to achieve the slow-release effect.

scholarly journals Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.

1997 ◽  
Vol 41 (5) ◽  
pp. 982-986 ◽  
Author(s):  
T P Kanyok ◽  
A D Killian ◽  
K A Rodvold ◽  
L H Danziger
Keyword(s):  
Healthy Subjects ◽  
Randomized Clinical Trials ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Multiple Drug ◽  
Time Data ◽  
Time Curve ◽  
First Order ◽  
Significant Difference

Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex. The objective of this randomized, parallel trial was to characterize the single-dose pharmacokinetics of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly allocated to receive a single, intramuscular aminosidine sulfate injection at a dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were collected over a 24-h period and used to determine aminosidine concentrations by high-performance liquid chromatographic assay. A one-compartment model with first-order input, first-order output, and a lag time (Tlag) and with a weighting factor of 1/y2 best described the data. Compartmental and noncompartmental pharmacokinetic parameters were estimated with the microcomputer program WinNonlin. One subject was not included (15-mg/kg group) because of the lack of sampling time data. On average, subjects attained peak concentrations of 22.4 +/- 3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each dosing group) had undetectable plasma aminosidine concentrations at 24 h. The dose-adjusted area under the concentration-time curve from 0 h to infinity of aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus 9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant differences (P > 0.05) were observed between dosing groups for peak aminosidine concentration in plasma, time to peak aminosidine concentration in plasma, Tlag, apparent clearance, renal clearance, elimination rate constant, and elimination half-life. A significant difference was observed for the volume of distribution (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing groups. Now that comparable pharmacokinetic profiles between dosing groups have been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic and pharmacodynamic modelling and randomized clinical trials in humans should be conducted.

scholarly journals Development of Paroxetine Hydrochloride Single Layer Controlled-Release Tablets Based on 32 Factorial Design

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 243 ◽  
Author(s):  
Yao Yang ◽  
Zhengwei Huang ◽  
Xuan Zhang ◽  
Jinyuan Li ◽  
Ying Huang ◽  
...  
Keyword(s):  
Controlled Release ◽  
Single Layer ◽  
Suicide Mortality ◽  
Pharmacokinetic Parameters ◽  
Release Mechanism ◽  
Time Curve ◽  
Layer Separation ◽  
Significant Difference ◽  
Paroxetine Hydrochloride ◽  
Controlled Release Tablets

Major depressive disorder (MDD) is one of the main contributors to disability and suicide mortality globally. Paroxetine hydrochloride (PHH) is the most potent antidepressant used for MDD treatment. Due to its reduced side effects PAXIL® CR is a widely-used controlled-release formulation of PHH. However, the complicated double-layer production of PAXIL® CR faces the risk of layer separation. In this study, PHH enteric coating single layer controlled-release tablets (PHH-EC-SLTs) were designed as a simplified substitution of PAXIL® CR through a rational formulation screening. The optimized PHH-EC-SLTs showed similar release behaviors in vitro to PAXIL® CR and the release profiles corresponded to a zero-order release model (R2 = 0.9958). Polymer matrix erosion was the main release mechanism, according to the fitting exponents n > 1 in the Korsmeyer-Pappas model. Crucial pharmacokinetic parameters including peak-reaching time (Tmax), peak concentration (Cmax) and the area under the blood level-time curve (AUC0-48) of PHH-EC-SLTs and PAXIL® CR had no significant difference (p > 0.05) and the relative bioavailability (F = 97.97%) of PHH-EC-SLTs demonstrated their similar pharmacokinetic profiles in vivo. In view of avoiding layer separation risk and simplifying the preparation processing, the self-made PHH-EC-SLTs could be considered as a safe and economic alternative to PAXIL® CR.

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