The effect of the area under the plasma concentration vs time curve and the maximum plasma concentration of esomeprazole on intragastric pH

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00683-09 ◽

2010 ◽

Vol 54 (1) ◽

pp. 411-417 ◽

Cited By ~ 28

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.

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

Canadian Journal of Gastroenterology ◽

10.1155/1997/910471 ◽

1997 ◽

Vol 11 (8) ◽

pp. 657-660 ◽

Cited By ~ 7

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.

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The Pharmacokinetics of Loratadine in Normal Geriatric Volunteers

Journal of International Medical Research ◽

10.1177/030006058801600106 ◽

1988 ◽

Vol 16 (1) ◽

pp. 50-60 ◽

Cited By ~ 14

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.

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Pharmacokinetic interaction between linagliptin and tadalafil in healthy Egyptian males using a novel LC–MS method

Bioanalysis ◽

10.4155/bio-2018-0097 ◽

2019 ◽

Vol 11 (14) ◽

pp. 1321-1336 ◽

Cited By ~ 2

Author(s):

Sara S Mourad ◽

Eman I El-Kimary ◽

Magda A Barary ◽

Dalia A Hamdy

Keyword(s):

Plasma Concentration ◽

Pharmacokinetic Interaction ◽

Volume Of Distribution ◽

Maximum Plasma Concentration ◽

Maximum Plasma ◽

Qtc Interval ◽

Qtc Prolongation ◽

Open Label ◽

Time Curve ◽

Concentration Time

Aim: Assessment of pharmacokinetic interaction between linagliptin (LNG) and tadalafil (TDL) in healthy males. Methods: First, a novel LC–MS method was developed; second, a Phase IV, open-label, cross-over study was performed. Volunteers took single 20-mg TDL dose on day 1 followed by wash out period of 2 weeks then multiple oral dosing of 5-mg/day LNG for 13 days. On day 13, volunteers were co-administered 20-mg TDL. Results: LNG and TDL single doses did not affect QTc interval. Smoking did not alter pharmacokinetics/pharmacodynamics of LNG and TDL. Co-administration of LNG with TDL resulted in TDL longer time to reach maximum plasma concentration (Tmax), decreased oral clearance (Cl/F) and oral volume of distribution (Vd/F), increased its maximum plasma concentration (Cmax), area under concentration-time curve (AUC), muscle pain and QTc prolongation. Conclusion: LNG and TDL co-administration warrants monitoring and/or TDL dose adjustment.

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Bioavailability of d-pseudoephedrine and Azatadine from a Repeat Action Tablet Formulation

Journal of International Medical Research ◽

10.1177/030006058201000210 ◽

1982 ◽

Vol 10 (2) ◽

pp. 122-125

Author(s):

C Lin ◽

J Lim ◽

S Symchowicz

Keyword(s):

Plasma Concentration ◽

Tablet Formulation ◽

Maximum Plasma Concentration ◽

Maximum Plasma ◽

Gas Liquid Chromatography ◽

Time Curve ◽

Conventional Tablet ◽

Cumulative Urinary Excretion ◽

Significant Difference ◽

Curve Maximum

The objective of this study was to compare in man the bioavailability of d-pseudoephedrine and azatadine from a repeat action tablet* formulation and from conventional tablets. The repeat action tablet, containing 1 mg of azatadine maleate in the coat, and 60 mg of d-pseudoephedrine sulfate in both the coat and the core, was given at 0 hour. A conventional tablet of 60 mg of d-pseudoephedrine sulfate was given at 0 and 4 hours and a conventional tablet of 1 mg of azatadine maleate was given at 0 hour. The plasma levels of d-pseudoephedrine were measured by gas-liquid chromatography and the amount of azatadine in the urine was determined by a mass fragmentographic procedure. The results showed that there were no statistically significant differences in the measured bioavailability parameters (area under plasma concentration-time curve, maximum plasma concentration and time to reach maximum plasma concentration) for pseudoephedrine from repeat action tablets and conventional d-pseudoephedrine sulfate tablets; neither was there any statistically significant difference in the cumulative urinary excretion of azatadine from the repeat action tablets and conventional azatadine maleate tablets (p > 0·10). These data clearly demonstrate the bioequivalence of the repeat action tablets and the conventional tablets of d-pseudoephedrine and azatadine.

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Preparation and pharmacokinetics of cefquinome sulfate liposomes in goats

Indian Journal of Animal Research ◽

10.18805/ijar.b-778 ◽

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.

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

British Journal Of Nutrition ◽

10.1017/s0007114510002709 ◽

2010 ◽

Vol 104 (11) ◽

pp. 1635-1640 ◽

Cited By ~ 40

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.

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Abstract P410: A Novel Curcumin Formulation, ASD-cur Suppressed Heart Failure After Myocardial Infarction In Rats

Circulation Research ◽

10.1161/res.129.suppl_1.p410 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Hidemichi Takai ◽

Tatsuya Morimoto

Keyword(s):

Heart Failure ◽

Plasma Concentration ◽

Cardiac Fibrosis ◽

Myocardial Cell ◽

Left Ventricular ◽

Cell Diameter ◽

Maximum Plasma ◽

Mrna Levels ◽

Time Curve ◽

Sd Rats

Introduction: Curcumin prevents the development of heart failure and is a potential treatment for heart failure. Although curcumin is known to be safe, its therapeutic efficiency is limited due to its low bioavailability. To overcome this problem, we developed ASD-Cur, an amorphous formulation of curcumin. In this study, we investigated the effect of ASD-Cur and compared it with Theracurmin ® , a colloidal submicron dispersion of curcumin. Methods: Male SD rats were orally administrated with ASD-Cur or Theracurmin ® (10 mg/kg curcumin). The plasma levels of curcumin were measured at 0.25, 0.5, 1, 2, 4 and 6 hours after administration. Twelve healthy volunteers, who had provided written informed consent, were administrated with ASD-Cur and Theracurmin ® containing 30 mg curcumin, and plasma curcumin concentrations were determined at 0.5, 1, 2, 4, and 8 hours. Next, male SD rats were subjected to MI or sham surgery. One week after surgery, the MI rats were randomly assigned to 4 groups: vehicle, ASD-Cur (0.2 mg/kg curcumin) or Theracurmin ® (0.2 or 0.5 mg/kg curcumin). Oral administration of these compounds was repeated for 6 weeks. After echocardiographic examinations, myocardial cell diameter, perivascular fibrosis, mRNA levels, and the acetylation of histone H3K9 were measured. Results: After administration in rats, the area under the plasma concentration-time curve ( AUC 0-6h ) and the maximum plasma concentration ( C max ) of ASD-Cur were 3.7-fold and 9.6-fold higher than those of Theracurmin ® , respectively. The AUC 0-8h and C max of ASD-Cur in humans were 3.4-fold and 5.4-fold higher than those of Theracurmin ® , respectively. Echocardiographic analysis showed that 0.2 mg/kg ASD-Cur and 0.5 mg/kg Theracurmin ® significantly improved the MI-induced deterioration of FS and left ventricular hypertrophy to the same extent. Both treatments significantly suppressed MI-induced increases in myocardial cell diameter, perivascular fibrosis, mRNA levels of hypertrophic markers and cardiac fibrosis, and acetylation of histone H3K9 to the same extent. Conclusion: These findings indicated that ASD-Cur has greater bioavailability than Theracurmin ® , and could exhibit greater therapeutic potency towards for MI-induced heart failure at a lower dose.

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Development of Level A In Vitro–Vivo Correlation for Electrosprayed Microspheres Containing Leuprolide: Physicochemical, Pharmacokinetic, and Pharmacodynamic Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics12010036 ◽

2020 ◽

Vol 12 (1) ◽

pp. 36

Author(s):

Dong-Seok Lee ◽

Dong Wook Kang ◽

Go-Wun Choi ◽

Han-Gon Choi ◽

Hea-Young Cho

Keyword(s):

Plasma Concentration ◽

Prediction Error ◽

Subcutaneous Administration ◽

In Vitro Dissolution ◽

Burst Release ◽

Maximum Plasma ◽

Time Curve ◽

In Vivo Dissolution

This study optimized the preparation of electrosprayed microspheres containing leuprolide and developed an in vitro–in vivo correlation (IVIVC) model that enables mutual prediction between in vitro and in vivo dissolution. The pharmacokinetic (PK) and pharmacodynamic (PD) study of leuprolide was carried out in normal rats after subcutaneous administration of electrosprayed microspheres. The parameters of the IVIVC model were estimated by fitting the PK profile of Lucrin depot® to the release compartment of the IVIVC model, thus the in vivo dissolution was predicted from the in vitro dissolution. From this correlation, the PK profile of leuprolide was predicted from the results of in vivo dissolution. The IVIVC model was validated by estimating percent prediction error (%PE) values. Among prepared microspheres, an optimal formulation was selected using the IVIVC model. The maximum plasma concentration and the area under the plasma concentration–time curve from zero to infinity from the predicted PK profile were 4.01 ng/mL and 52.52 h·ng/mL, respectively, and from the observed PK profile were 4.14 ng/mL and 56.95 h·ng/mL, respectively. The percent prediction error values of all parameters did not exceed 15%, thus the IVIVC model satisfies the validation criteria of the Food and Drug Administration (FDA) guidance. The PK/PD evaluation suggests that the efficacy of OL5 is similar to Lucrin depot®, but the formulation was improved by reducing the initial burst release.

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