scholarly journals Multilayer-Coated Tablet of Clopidogrel and Rosuvastatin: Preparation and In Vitro/In vivo Characterization

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 313
Author(s):  
Ki-Soo Seo ◽  
Hyo-Kyung Han
Keyword(s):  
Plasma Concentration ◽  
Coating Layer ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Dissolution Profile ◽  
Reference Drug ◽  
Acid Degradation ◽  
Glyceryl Behenate ◽  
Coated Tablet ◽  
Core Tablet

The acid lability of rosuvastatin hinders the preparation of mixed combination formulations of rosuvastatin with acidic drugs such as clopidogrel. Therefore, the purpose of this study was to develop a multilayer-coated tablet that avoids physicochemical interactions between rosuvastatin and clopidogrel. Among the tested hydrophobic materials, glyceryl behenate was most effective at inhibiting the production of lactone, the acid degradation product of rosuvastatin. Therefore, the multilayer-coated tablet included a hydrophobic separation layer consisting of glyceryl behenate between the clopidogrel core tablet and the rosuvastatin coating layer. In order to prevent delayed dissolution by the stable hydrophobic separation layer, crospovidone was added into the clopidogrel core tablet as an effective disintegrant. Copovidone was also added to the coating layer of rosuvastatin, achieving a dissolution profile comparable to that of the reference drug, Crestor®. The resulting multilayer-coated tablet exhibited similar pharmacokinetic profiles to those of reference drugs (Plavix® and Crestor®) in beagle dogs, and there was no statistically significant difference in the maximum plasma concentration (Cmax), the time to reach the maximum plasma concentration (Tmax), or the area under the plasma-concentration time curve (AUC) between the test and reference formulations. The storage stability tests showed that the amounts of acid degradation products and total impurities were comparable to that of the reference drug. In conclusion, the present study successfully developed a stable multilayer-coated tablet containing both clopidogrel and rosuvastatin that may improve the patient compliance in combination therapy for cardiovascular diseases.

Preparation and pharmacokinetics of cefquinome sulfate liposomes in goats

2018 ◽  
Author(s):  
Haigang Wu ◽  
Jinni Liu ◽  
Gugangke Xu ◽  
Zhaowei Ye ◽  
Jicheng Liu and Benchi Yi
Keyword(s):  
Plasma Concentration ◽  
Particle Diameter ◽  
Entrapment Efficiency ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Average Particle ◽  
Average Particle Diameter ◽  
Ethanol Injection ◽  
Elimination Half ◽  
Time Point

We evaluated the pharmacokinetics of cefquinome sulfate (CEF) liposomes in eight healthy goats following intramuscular administration at 4 mg/kg. The average particle diameter of CEF liposomes prepared by the ethanol injection method was 335nm with a CEF entrapment efficiency of 69.56%. The elimination half-life (t1/2b) of CEF liposomes was 33.04h compared with 16.21 h for CEF injected without carrier (p less than 0.05). The area under the concentration curve (AUC) for CEF liposomes was approximately three-times greater than for CEF alone (P less than 0.05). The time-point of maximum plasma concentration of the drug (Tp) and the maximum plasma concentration (Cmax) were 4.38 h and 1.99 ìg/mL for CEF liposomes, compared with 1.86 h and 3.55 ìg/mL for CEF without carrier, respectively. 

scholarly journals Plasma appearance and correlation between coffee and green tea metabolites in human subjects

2010 ◽  
Vol 104 (11) ◽  
pp. 1635-1640 ◽  
Author(s):  
Mathieu Renouf ◽  
Philippe Guy ◽  
Cynthia Marmet ◽  
Karin Longet ◽  
Anne-Lise Fraering ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Green Tea ◽  
Phenolic Acids ◽  
Human Subjects ◽  
Coffee Consumption ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Isoferulic Acid ◽  
Long Time ◽  
High Level

Coffee and green tea are two of the most widely consumed hot beverages in the world. Their respective bioavailability has been studied separately, but absorption of their respective bioactive phenolics has not been compared. In a randomised cross-over design, nine healthy subjects drank instant coffee and green tea. Blood samples were collected over 12 h and at 24 h to assess return to baseline. After green tea consumption, ( − )-epigallocatechin (EGC) was the major catechin, appearing rapidly in the plasma; ( − )-EGC gallate (EGCg) and ( − )-epicatechin (EC) were also present, but ( − )-EC gallate and C were not detected. Dihydroferulic acid and dihydrocaffeic acid were the major metabolites that appeared after coffee consumption with a long time needed to reach maximum plasma concentration, suggesting metabolism and absorption in the colon. Other phenolic acid equivalents (caffeic acid (CA), ferulic acid (FA) and isoferulic acid (iFA)) were detected earlier, and they peaked at lower concentrations. Summations of the plasma area under the curves (AUC) for the measured metabolites showed 1·7-fold more coffee-derived phenolic acids than green tea-derived catechins (P = 0·0014). Furthermore, we found a significant correlation between coffee metabolites based on AUC. Inter-individual differences were observed, but individuals with a high level of CA also showed a correspondingly high level of FA. However, no such correlation was observed between the tea catechins and coffee phenolic acids. Correlation between AUC and maximum plasma concentration was also significant for CA, FA and iFA and for EGCg. This implies that the mechanisms of absorption for these two classes of compounds are different, and that a high absorber of phenolic acids is not necessarily a high absorber of catechins.

scholarly journals Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine.

1997 ◽  
Vol 41 (8) ◽  
pp. 1765-1769 ◽  
Author(s):  
S C Chien ◽  
A T Chow ◽  
M C Rogge ◽  
R R Williams ◽  
C W Hendrix
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Plasma Concentration ◽  
The Body ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Cell Counts ◽  
Pharmacokinetic Profiles ◽  
Study Results ◽  
Immunodeficiency Virus

This phase I, double-blind, randomized, placebo-controlled, parallel-design study was conducted to evaluate the safety and pharmacokinetics of levofloxacin in human immunodeficiency virus (HIV)-infected subjects concomitantly receiving a stable regimen of zidovudine (AZT). Sixteen HIV-infected males with CD4-cell counts ranging from 100 to 550 and not experiencing significant AZT intolerance were enrolled. Subjects received levofloxacin (350 mg of levofloxacin hemihydrate) or a placebo (eight subjects per treatment group) as a single oral dose on day 1, multiple doses every 8 h from days 3 to 9, and a single dose on day 10. On days 1 and 10, an AZT dose (100 mg) was administered concurrently with the study drug. In between these doses, AZT was administered according to the regimen used by the subject prior to entering the study up to a maximum of 500 mg/day. Plasma levofloxacin concentrations were monitored for 36 h after levofloxacin dosing on day 1, immediately prior to the morning doses on days 3 to 9, and for 72 h after dosing on day 10. Plasma AZT concentrations were monitored on day 0 for baseline (for 6 h after the AZT dose) and for 4 h after the AZT doses on days 1 and 10. Levofloxacin was rapidly absorbed (time to maximum plasma concentration, approximately 1.0 h) and extensively distributed in the body with an apparent volume of distribution of approximately 104 liters (approximately 1.34 liters/kg). Steady-state conditions on day 10 were confirmed. Pharmacokinetic profiles of levofloxacin from single doses and multiple (three-times-daily) doses were similar, with a moderate accumulation (observed day 10-to-day 1 ratio of the maximum plasma concentration, approximately 185% versus expected 169%; for the corresponding ratio of the area under the concentration-time curve from 0 to 8 h [AUC(0-8)], the values were observed 217% versus expected 169%) at steady state. Mean average steady-state peak plasma concentration, plasma levofloxacin concentration at the end of the dosing interval, AUC(0-8), terminal half-life, and total body clearance were 7.06 microg/ml, 3.62 microg/ml, 37.4 microg x h/ml, 7.2 h, and 9.4 liters/h (0.12 liters/h/kg), respectively. Pharmacokinetic profiles of levofloxacin in HIV-infected patients did not appear to be affected by the concomitant administration of AZT; nor were AZT pharmacokinetics altered by levofloxacin. Oral administration of 350 mg of levofloxacin hemihydrate every 8 h appeared to be well tolerated by the subjects. There were no apparent differences in adverse events between the two treatment groups. There were no clinically significant changes from baseline in any laboratory parameter or vital sign following treatments observed in this study. The study results suggest that there is no need for levofloxacin dosage adjustment in HIV-seropositive subjects who concomitantly receive AZT.

scholarly journals Investigations on the Influence of Zidovudine in the Pharmacokinetics of Isoniazid and Its Hepatotoxic Metabolites in Rats

2017 ◽  
Vol 32 (1) ◽  
pp. 9-18
Author(s):  
Raghu Ramanathan ◽  
Karthikeyan Sivanesan
Keyword(s):  
Plasma Concentration ◽  
Drug Interactions ◽  
Bacterial Infections ◽  
Plasma Clearance ◽  
Combined Therapy ◽  
Maximum Plasma Concentration ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Group I ◽  
Pharmacokinetic Drug

The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites. Seventy two rats were randomly divided into two major groups with their sub-groups each comprising 6 animals. The Group I received INH alone at a dose of 25 mg/kg; b.w and Group II received AZT (50 mg/kg; b.w) along with INH orally. Pharmacokinetic studies of INH and its metabolites i.e., acetyl hydrazine (ACHY) and hydrazine (HYD) shows that INH and ACHY attains maximum plasma concentration ( Cmax) within 30 minutes and HYD attains Cmax at 1 hour after INH administration and all these analytes disappear from plasma within 4 hours. Pharmacokinetic studies also revealed that AZT treatment did not showed any drug-drug interactions and have no effect on the T1/2, plasma clearance, AUC, Cmax and Tmax of INH and its hepatotoxic metabolites.

Comparative Bioavailability of a Microsize and Ultramicrosize Griseofulvin Formulation in Man

1982 ◽  
Vol 10 (4) ◽  
pp. 274-277 ◽  
Author(s):  
C Lin ◽  
J Lim ◽  
C DiGiore ◽  
R Gural ◽  
bS Symchowicz
Keyword(s):  
Plasma Concentration ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Comparative Bioavailability ◽  
Plasma Concentration Time Curve ◽  
Randomized Crossover Study ◽  
Curve Maximum

The bioavailability of 500 mg of a microsize formulation of griseofulvin has been compared to two new ultramicrosize griseofulvin formulations, two 165 mg tablets and a 330 mg tablet, in sixteen healthy, male, volunteers in a randomized crossover study design. Based on the griseofulvin plasma levels measured at specified times over a 48-hour period, the major bioavailability parameters (i.e., area under plasma concentration-time curve, maximum plasma concentration, and time to reach maximum plasma concentration) were determined and statistically evaluated. The results showed that one 330 mg ultramicrosize tablet is bioequivalent to two 165 mg ultramicrosize griseofulvin tablets and that either ultramicrosize griseofulvin dosage regimen is bioequivalent to 500 mg of the microsize griseofulvin formulation.

scholarly journals Multiple-Dose Safety, Tolerability, and Pharmacokinetics of Oral Nemonoxacin (TG-873870) in Healthy Volunteers

2010 ◽  
Vol 54 (1) ◽  
pp. 411-417 ◽  
Author(s):  
David T. Chung ◽  
Cheng-Yuan Tsai ◽  
Shu-Jen Chen ◽  
Li-Wen Chang ◽  
Chi-Hsin R. King ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Volunteers ◽  
Bacterial Infections ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Atypical Pathogens ◽  
Plasma Concentration Time Curve

ABSTRACT Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with broad-spectrum activities against Gram-positive and Gram-negative aerobic, anaerobic, and atypical pathogens, as well as against methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus, and multiple-resistant bacterial pathogens. We conducted a randomized, double-blind, placebo-controlled, dose-escalating study to ascertain the safety, tolerability, and pharmacokinetics of nemonoxacin. We enrolled 46 healthy volunteers and used a once-daily oral-dosing range of 75 to 1,000 mg for 10 days. Additionally, the food effect was evaluated in subjects in the 500-mg cohort. Nemonoxacin was generally safe and well tolerated, with no significant changes in the clinical laboratory tests or electrocardiograms. Adverse effects, including headache, contact dermatitis, and rash, were mild and resolved spontaneously. Nemonoxacin was rapidly absorbed within 2 h postdosing, and generally, a steady state was reached after 3 days. The maximum plasma concentration and the area under the plasma concentration-time curve were dose proportional over the dosing range. The elimination half-life was approximately 7.5 h and 19.7 h on days 1 and 10, respectively. Approximately 37 to 58% of the drug was excreted in the urine. Food affected the pharmacokinetics, with decreases in the maximum plasma concentration and area under the plasma concentration-time curve of 46% and 27%, respectively. However, the free AUC/MIC90 of nemonoxacin was more than 100 under both the fasting and fed conditions, predicting the efficacy of nemonoxacin against most of the tested pathogens. In conclusion, the results support further clinical investigation of once-daily nemonoxacin administration for antibiotic-sensitive and antibiotic-resistant bacterial infections.

scholarly journals Pharmacokinetics and Pharmacodynamics during Treatment with the Omeprazole 20 mg Enteric-Coated Tablet and 20 mg Capsule in Asymptomatic Duodenal Ulcer Patients

1997 ◽  
Vol 11 (8) ◽  
pp. 657-660 ◽  
Author(s):  
ABR Thomson ◽  
P Kirdeikis ◽  
R Lastiwka ◽  
K Rohss ◽  
P Sinclair ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Maximum Plasma ◽  
Intragastric Ph ◽  
Time Curve ◽  
Enteric Coated Tablet ◽  
Coated Tablet ◽  
Enteric Coated ◽  
Repeated Dosing

This study compared the 24 h intragastric pH profile and bioavailability at repeated dosing conditions of the omeprazole 20 mg enteric-coated tablet versus the 20 mg capsule. Forty duodenal ulcer patients in asymptomatic remission completed this randomized open two-way crossover study. Omeprazole 20 mg tablets or capsules were administered for seven days in each period. A 24 h pH recording was performed before the start of treatment and on day 7 of each treatment period. Plasma concentrations of omeprazole were determined 24 h after the dose. The treatment periods were separated by two to four weeks. The difference in percentage of time with pH of at least 3 was less than 16% in favour of the tablet (not significant). The estimated mean area under the plasma concentration-time curve as well as the maximum plasma concentration (Cmax) for omeprazole were 18% and 41% higher, respectively, for the tablet versus the capsule, with the latter percentage being statistically significant. The time to reach Cmax(tmax) with the tablet was, on average, about 0.5 h longer than to reach the tmaxof the capsule. This study indicates that the enteric-coated tablet formulation of omeprazole is biodynamically equivalent to the capsule regarding their effects on intragastric pH during repeated dosing.

The Pharmacokinetics of Loratadine in Normal Geriatric Volunteers

1988 ◽  
Vol 16 (1) ◽  
pp. 50-60 ◽  
Author(s):  
J. Hilbert ◽  
V. Moritzen ◽  
A. Parks ◽  
E. Radwanski ◽  
G. Perentesis ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
High Performance ◽  
The Elderly ◽  
Maximum Plasma Concentration ◽  
Pharmacokinetic Analysis ◽  
Maximum Plasma ◽  
Open Label ◽  
Post Dose ◽  
Time Curve ◽  
Concentration Time

The pharmacokinetics of loratadine, a non-sedating anti-histamine, were studied in 12 normal geriatric volunteers. In an open label fashion, each volunteer received one 40 mg loratadine capsule. Blood was collected prior to and at specified times (up to 120 h) after dosing. Plasma loratadine concentrations were determined by a specific radioimmunoassay and those of an active metabolite, descarboethoxyloratadine, by high performance liquid chromatography. Concentrations of loratadine in the disposition phase were fitted to a biexponential equation and those of descarboethoxyloratadine to either a monoexponential or biexponential equation for pharmacokinetic analysis. Loratadine was rapidly absorbed, reaching a maximum plasma concentration of 50.5 ng/ml at 1.5 h after dosing. The disposition half-lives of loratadine in the distribution and elimination phases were 1.5 and 18.2 h, respectively. The area under the plasma concentration–time curve, was 146.7 h·ng/ml. Descarboethoxyloratadine had a maximum plasma concentration of 28.0 ng/ml at 2.9 h post-dose and an area under the concentration–time curve of 394.9 h·ng/ml. Its disposition half-lives in the distribution and elimination phases were 2.8 and 17.4 h, respectively. Comparison of these data with those from a previous study of loratadine in young adults showed no clear differences in the disposition half-lives between the two groups. The clearance of loratadine tends to be lower in the elderly, but inter-individual variation within each age group appears greater than any age effect.

scholarly journals Simultaneous Determination and Pharmacokinetic Study of Quercetin, Luteolin, and Apigenin in Rat Plasma after Oral Administration of Matricaria chamomilla L. Extract by HPLC-UV

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaoxv Dong ◽  
Wei Lan ◽  
Xingbin Yin ◽  
Chunjing Yang ◽  
Wenping Wang ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Oral Administration ◽  
Simultaneous Determination ◽  
Rat Plasma ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Matricaria Chamomilla ◽  
The Mean ◽  
Lower Limits

A simple and sensitive HPLC-UV method has been developed for the simultaneous determination of quercetin, luteolin, and apigenin in rat plasma after oral administration of Matricaria chamomilla L. extract. The flow rate was set at 1.0 ml/min and the detection wavelength was kept at 350 nm. The calibration curves were linear in the range of 0.11–11.36 μg/ml for quercetin, 0.11–11.20 μg/ml for luteolin, and 0.11–10.60 μg/ml for apigenin, respectively. The intraday and interday precisions (RSD) were less than 8.32 and 8.81%, respectively. The lower limits of quantification (LLOQ) of the three compounds were 0.11 μg/ml. The mean recoveries for quercetin, luteolin, and apigenin were 99.11, 95.62, and 95.21%, respectively. Stability studies demonstrated that the three compounds were stable in the preparation and analytical process. The maximum plasma concentration (Cmax) was 0.29 ± 0.06, 3.04 ± 0.60, and 0.42 ± 0.10 μg/ml, respectively. The time to reach the maximum plasma concentration (Tmax) was 0.79 ± 0.25, 0.42 ± 0.09, and 0.51 ± 0.13 h, respectively. The validated method was successfully applied to investigate the pharmacokinetics study of quercetin, luteolin, and apigenin in rat plasma after oral administration of M. chamomilla extract.

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