scholarly journals Bioavalaibility and pharmacokinetic comparison of two formulations of metformin 850 mg tablets in healthy Colombian volunteers

2011 ◽  
pp. 81-87 ◽  
Author(s):  
Gloria Holguín ◽  
Fanny Cuesta ◽  
Rosendo Archbold ◽  
Margarita Restrepo ◽  
Sergio Parra ◽  
...  
Keyword(s):  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Logarithmic Mean ◽  
Reference Formulation ◽  
Anova Analysis ◽  
Double Blind ◽  
Metformin Concentration ◽  
The Mean ◽  
Carry Over ◽  
Logarithmic Ratio

Purpose: The aim of this study was to compare the bioavailability of two formulations of metformin 850 mg tablets: Glucophage® from Merck Santè laboratories (reference product) and Metformin from Winthrop Pharmaceuticals de Colombia SA (test product) in healthy Colombian volunteers. Methods: A random, double blind, two-period, two-week wash out period, crossover study was performed in 24 healthy male and female volunteers for a single 850-mg dose of metformin tablets administrated with 240 ml of water after 12 hours of fasting. Once the drug was administrated, blood samples were collected before and within 24 hour, and plasma metformin concentration was determined by using a validated HPLC method. Pharmacokinetic parameters such as Cmax, AUC0-96h, AUC0-∞, and Tmax were determined. The formulations were considered bioequivalent if the logarithmic mean ratios of ln-transformed Cmax and AUC0-∞ values were within the equivalence range of 80%-125%. Results: ANOVA analysis of the ln-transformed Cmax and AUC0-∞ indicated that none of the effects examined (formulation, period, within and between-subjet variances and carry over) was statistically significant. The mean (±SD) of Cmax 1217.38 (± 251.72) ng/ml vs. 1305.25 (± 301.06) ng/ml, AUC0-96h 1363.49 (± 315.51) ng.h/ml vs. 1584.82 (± 368.75) ng.h/ml, AUC0-∞, 7155.75 (± 1440.74) ng.h/ml vs. 7777.08 (± 1896.49) ng.h/ml, and Tmax 2.57 (± 0.93) h vs. 2.22 (± 0.94) h were obtained with test and reference formulations, respectively. These pharmacokinetic parameters presented differences with the results from other published papers. The 90% confidence interval of the logarithmic ratio of AUC0-∞ and Cmax was within the range of 80-125%. Conclusions: In this study in healthy Colombian volunteers, a single 850-mg dose of metformin tablet test formulation met the criteria for bioequivalence to the reference formulation based on pharmacokinetic parameters AUC0-∞ and Cmax.

scholarly journals DEVELOPMENT AND VALIDATION OF BIOANALYTICAL HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF CILNIDIPINE AND NEBIVOLOL IN HUMAN PLASMA

2017 ◽  
Vol 9 (10) ◽  
pp. 253
Author(s):  
Aruna G. ◽  
Bharathi K ◽  
Kvsrg Prasad
Keyword(s):  
Human Plasma ◽  
Analytical Method ◽  
Internal Standard ◽  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Simultaneous Estimation ◽  
Time Data ◽  
Bioanalytical Method Validation ◽  
Limit Of Quantitation ◽  
The Mean

Objective: To develop and validate a modified isocratic reversed-phase high performance liquid chromatographic (RP-HPLC) method for determination of cilnidipine and nebivolol in human plasma to be used for pharmacokinetic studies.Methods: The drug was extracted from plasma samples by direct protein precipitation technique using acetonitrile. Amlodipine was used as internal standard (IS). Samples were analyzed on BDS C18 column (250 x 4.6 mm, 5 µm), applying ortho phosphoric acid (0.1%): Acetonitrile, at a ratio of 45:55 v/v in isocratic mode as a mobile phase at a flow rate of 1 ml/min to attain adequate resolution. Separations were performed at room temperature and monitored at a wavelength of 260 nm after injection of 50μl samples into the HPLC system. The analytical method was validated according to FDA bioanalytical method validation guidance. The method was applied for pharmacokinetic study of cilnidipine and nebivolol tablets-10 mg and 5 mg were administered as a single dose to 6 healthy male rabbits under fasting condition. Twelve blood samples were withdrawn from each rabbit over 24 h periods. From the plasma concentration-time data of each individual, the pharmacokinetic parameters; Cmax, Tmax, AUC0-t and AUC0-∞ were calculated.Results: A peak area was obtained for cilnidipine and nebivolol at 3.943 and 4.719 min retention time respectively. Linearity was established at a concentration range of 0.20-20 μg/ml (r2=0.999, n=8) for cilnidipine and 0.02-2 μg/ml (r2=0.999, n=8) for nebivolol. The lower limit of quantitation (LLOQ) was identifiable and reproducible at 0.2μg/ml for cilnidipine and 0.02 μg/ml for nebivolol. The coefficients of variation (%cv) of the intra-day and inter-day precision of cilnidipine at 600, 1000 and 1600ng/ml levels were found to be 6.90%, 6.19%, 5.22%; and 7.74%, 6.54%, 5.77%, respectively, which are lower than the accepted criteria limits (15-20 %). The mean recovery (%) cilnidipine at 600, 1000, and 1600ng/ml was found to be 101.03%, 99.27% and 104.87%, and for nebivolol 60, 100, and 160 ng/ml was found to be 106.13%, 107.03% and 98.06% respectively. Stability at different conditions and in autosampler was also established. The mean pharmacokinetic parameters; Cmax, Tmax, AUC0-t and AUC0-∞ were 6 ng/ml, 2 hr, 96.76 mg. hr/ml, 63.45 mg. hr/ml for cilnidipine and 5.8ng/ml, 2hr, 74.78 mg. hr/ml, 100.25 mg. hr/ml for nebivolol respectively.Conclusion: The present analytical method was found to be specific, sensitive, accurate and precise for quantification of cilnidipine and nebivolol in human plasma. It can be successively applied for pharmacokinetics, bioavailability and bioequivalence studies.

scholarly journals Pharmacokinetics of a Once-Daily Oral Dose of Moxifloxacin (Bay 12-8039), a New Enantiomerically Pure 8-Methoxy Quinolone

1999 ◽  
Vol 43 (11) ◽  
pp. 2793-2797 ◽  
Author(s):  
John T. Sullivan ◽  
Marilyn Woodruff ◽  
John Lettieri ◽  
Vipin Agarwal ◽  
George J. Krol ◽  
...  
Keyword(s):  
High Performance ◽  
Vital Signs ◽  
Blood Chemistry ◽  
Controlled Study ◽  
Pharmacokinetic Parameters ◽  
Fluorometric Detection ◽  
Double Blind ◽  
Time Curve ◽  
Once Daily ◽  
The Mean

ABSTRACT The pharmacokinetics, safety, and tolerability of oral moxifloxacin, a new 8-methoxy quinolone, were assessed in a randomized, double-blind, placebo-controlled study in which healthy male and female volunteers received either 400 mg of moxifloxacin once daily (n = 10) or a placebo once daily (n = 5) for 10 days. Plasma moxifloxacin concentrations on days 1 and 10 were measured by high-performance liquid chromatography and fluorometric detection. Standard pharmacokinetic parameters were estimated by noncompartmental methods. Natural logarithmic estimates for each pharmacokinetic variable of each subject were analyzed by a two-way analysis of variance. Hematology, blood chemistry, vital signs, and adverse events were monitored, and electrocardiograms (ECG) were performed. Plasma moxifloxacin concentrations of predicted therapeutic relevance were achieved in this study. For day 1, the mean maximum concentration of drug in serum (C max) and the area under the concentration-time curve from 0 to 24 h (AUC0–24) were 3.4 mg/liter and 30.2 mg · h/liter, respectively. Corresponding means on day 10 were 4.5 mg/liter and 48 mg · h/liter, respectively. On day 10, the mean elimination half-life was approximately 12 h. Plasma moxifloxacin concentrations exceeded the MIC for Streptococcus pneumoniae throughout the 24-h dosing period. The day 1 and day 10 mean AUC/MIC ratios were 121 and 192, respectively, and the meanC max/MIC ratios were 13 and 18, respectively. Moxifloxacin was well tolerated; no clinically relevant changes in the standard laboratory tests, vital signs, or ECG were observed. Pharmacokinetic parameters demonstrated linearity, and estimates of pharmacokinetic/pharmacodynamic ratios (AUC/MIC andC max/MIC) indicate that the regimen of 400-mg once daily should be effective for treating a variety of infections. Moxifloxacin was found to be safe and well tolerated in healthy volunteers when it was given as a single daily 400-mg dose for 10 days.

Pharmacokinetic Study of Two Oral Formulations of Levofloxacin in Healthy Male Volunteersl

1970 ◽  
Vol 5 (1) ◽  
pp. 39-45
Author(s):  
Maruf Mohammad Akbor ◽  
Rebeka Sultana ◽  
Mohammad Abul Kalam Azad ◽  
AHM Mahbub Latif ◽  
Md. Ashik Ullah ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Reference Formulation ◽  
P Values ◽  
Acceptable Range ◽  
Oral Formulations ◽  
The Mean ◽  
The Difference ◽  
Extent Of Absorption

The objective of this study was to compare different pharmacokinetic parameters of a local (“X”) and reference (Tavanic) formulations of levofloxacin 250 mg tablets after oral administration of a single dose under fasting condition. Thirteen blood samples were collected from each of the eight Bangladeshi healthy male volunteers over 24 hours after oral administration of the drugs. Serum levofloxacin concentrations were determined by HPLC assay using UV detection, and pharmacokinetic parameters were determined by the non-compartmental method. Mean ± SD of Cmax, AUC0-24, AUC0-α, Tmax, t1/2, kel, were 4.33 ± 1.16 and 4.56 ± 1.51 ?g/mL, 45.90 ± 8.74 and 37.77 ± 9.94 hr-?g /mL, 79.94 ± 32.80 and 66.85 ± 35.43 hr-?g/mL, 1.22 ± 0.49 and 1.28 ± 0.41, 19.90 ± 11.49 and 21.00 ± 16.39 hr, 0.04 ± 0.02 and 0.05 ± 0.03 hr -1 for the local (“X”) and reference formulation, respectively. From the paired t-test, the p-values for two formulations were found to be 0.182, 0.412 and 0.725 for AUC0-24, AUC0-α, and Cmax respectively. The 90% confidence intervals of the mean of the difference between log-transformed values for Cmax were almost within the bioequivalence accepted range of 80% to 125%, namely: (78.90%, 118.36%); but for AUC0-24 and AUC0-α the values were are beyond the acceptable range. (100.83%, 146.52%) and (94.34%, 157.89%) respectively. The results indicate that the two formulations are not bioequivalent for both the rate and extent of absorption. Key words: Levofloxacin, pharmacokinetic, bioavailability, bioequivalence Dhaka Univ. J. Pharm. Sci. Vol.5(1-2) 2006 The full text is of this article is available at the Dhaka Univ. J. Pharm. Sci. website

scholarly journals A Simple RP?HPLC Method for the Determination of Cefdinir in Human Serum: Validation and Application in a Pharmacokinetic Study with Healthy Bangladeshi Male Volunteers

2012 ◽  
Vol 10 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Golam Mortuza Shahed ◽  
Md Ashik Ullah ◽  
Abdullah Al Abdullah Al ◽  
Maizbha Uddin Ahmed ◽  
Mohammad Safiqul Islam ◽  
...  
Keyword(s):  
Human Serum ◽  
Internal Standard ◽  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Dihydrogen Phosphate ◽  
Serum Samples ◽  
Limit Of Quantification ◽  
Rp Hplc ◽  
Male Volunteers ◽  
The Mean

In the present study, a simple RP?HPLC method with UV detection has been validated to determine cefdinir concentrations in human serum samples and applied to determine the pharmacokinetic parameters of cefdinir in healthy Bangladeshi male volunteers. The mobile phase consisting of a mixture of 0.2 M sodium dihydrogen phosphate buffer (pH 3.2 ± 0.05 adjusted with o-phosphoric acid) and methanol at a ratio of 70:30 (v/v), was pumped at a flow rate of 1.0 ml/min through the C18 column at room temperature and the chromatographic separation was monitored at a wavelength of 254 nm with a sensitivity of 0.0001 AUFS. Cefaclor was used as internal standard. The developed method was selective and linear for cefdinir concentrations ranging from 0.05 to 5 ?g/ml for serum samples. The lower limit of quantification was defined as the lowest concentration on the calibration curve (0.05 ?g/ml) for which an acceptable accuracy of 111.60 % and a precision of 7.65 % were obtained, while the minimum detectable quantity of cefdinir was found to be 0.02 ?g/ml. The intra-day and inter-day coefficient of variation (CV) at 0.05 ?g/ml were 7.65% and 9.72%, respectively. The average recovery of cefdinir from serum was 96.43 %. Acceptable results were obtained during stability study. The mean Cmax of cefdinir was found to be 1.42 ± 0.53 ?g/ml attained at a mean Tmax of 3.81 ± 0.96 hr. The mean elimination half-life was 2.03 hours. This method proved to be simple, accurate and precise for pharmacokinetic and bioequivalence studies of cefdinir.   DOI: http://dx.doi.org/10.3329/dujps.v10i2.11790   Dhaka Univ. J. Pharm. Sci. 10(2): 109-116, 2011 (December)

scholarly journals ​Pharmacokinetic Disposition and Residue Status of Tilmicosin in Broiler Chicken after ‘In-Crop’ and ‘In-Water’ Administration

2021 ◽  
Author(s):  
Sakthivel Duraisamy ◽  
Ramesh Srinivasan ◽  
Vinothini Prabhakaran ◽  
Karthick Venkatesh ◽  
Porteen . ◽  
...  
Keyword(s):  
Drinking Water ◽  
High Performance ◽  
Broiler Chicken ◽  
Plasma Concentrations ◽  
Mycoplasma Gallisepticum ◽  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
The Mean ◽  
Water Administration

Background: The aim is to study the pharmacokinetics and tissue residue status of tilmicosin after administration through ‘in-crop’ and ‘in-water’ routes and compare the effectiveness of the two routes and establish a suitable dosage regimen for treating Mycoplasma gallisepticum infection in broiler chicken. Methods: The plasma pharmacokinetic disposition of tilmicosin in broiler chicken was investigated after administration orally by direct deposition at crop (25 mg/kg body weight) or drinking water (40 mg/kg b.wt.). Residues of tilmicosin in tissues of broiler chicken were assayed. The plasma and tissue concentrations of tilmicosin were analyzed by reverse-phase high-performance liquid chromatography (HPLC) method. The plasma concentration-time data was described by the non-compartmental model for both routes and pharmacokinetic parameters were calculated. The data were statistically analyzed by Mann-Whitney U test Conclusion: The mean plasma concentrations of tilmicosin in two routes tested (in-crop, in-water) were effective above MIC reported for Mycoplasma gallisepticum (0.05 µg/ml) up to 24 h. In addition, the drug residue in lungs was found at desirable concentration up to 22 days. However, residues of tilmicosin in tissues were above the advocated maximum residue limit (MRL) till 18th day in muscle and liver and till 22nd day in kidney. The results of the study indicate that the antimycoplasmal drug tilmicosin can be therapeutically efficacious after administration in crop as well as in drinking water.

scholarly journals A Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2967 ◽  
Author(s):  
Katharina Knaub ◽  
Tina Sartorius ◽  
Tanita Dharsono ◽  
Roland Wacker ◽  
Manfred Wilhelm ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Bioavailability ◽  
Cannabis Sativa ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Reference Formulation ◽  
Double Blind ◽  
Study Objective

Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa, shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0–8h/AUC0–24h compared to the reference formulation. Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h). Subgroup analysis demonstrated a higher bioavailability in women compared to men. This difference was seen for MCT-CBD while SEDDS-CBD mitigated this gender effect. Overall, SEDDS-CBD showed a significant improvement for all determined pharmacokinetic parameters: increased CBD plasma values (Cmax), favorably enhanced bioavailability (AUC) and fast absorption (Tmax). No safety concerns were noted following either administration.

The Antiaggressive Action of Combined Haloperidol-Propranolol Treatment in Schizophrenia

2000 ◽  
Vol 5 (4) ◽  
pp. 312-325 ◽  
Author(s):  
Gadi Maoz ◽  
Daniel Stein ◽  
Sorin Meged ◽  
Larisa Kurzman ◽  
Joseph Levine ◽  
...  
Keyword(s):  
Rating Scales ◽  
Double Blind ◽  
Propranolol Group ◽  
Schizophrenic Patients ◽  
Propranolol Treatment ◽  
Simultaneous Decrease ◽  
The Mean ◽  
Haloperidol Treatment ◽  
To Receive ◽  
Drug Free

Psychopharmacological interventions for managing aggression in schizophrenia have thus far yielded inconsistent results. This study evaluates the antiaggressive efficacy of combined haloperidol-propranolol treatment. Thirty-four newly admitted schizophrenic patients were studied in a controlled double-blind trial. Following a 3-day drug-free period and 7 days of haloperidol treatment, patients were randomly assigned to receive either haloperidol-propranolol or haloperidol-placebo for eight consecutive weeks. Doses of medications were adjusted as necessary; biperiden was administered if required. Rating scales were applied to assess aggression, anger, psychosis, depression, anxiety and extrapyramidal symptoms. The mean daily dose of haloperidol was 21 mg (SD = 6.4) in the research group and 29 mg (SD = 6.9) in the controls. Mean and maximal daily doses of propranolol were 159 mg (SD = 61) and 192 mg (SD = 83), and of placebo, 145 mg (SD = 50) and 180 mg (SD = 70), respectively. Compared with the controls, the scores for the research patients decreased significantly from baseline, particularly after 4 weeks of treatment, for some dimensions of anger, psychosis, anxiety, and neuroleptic-induced parkinsonism. A tendency for reduced aggression was shown in the combined haloperidol-propranolol group for some dimensions but not others. These patients also required significantly less biperiden. The tendency toward elevated antiaggressive effect of combined haloperidol-propranolol treatment compared to haloperidol alone may be explained by a simultaneous decrease in aggression, psychotic symptomatology, and anxiety.

The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

1995 ◽  
Vol 74 (04) ◽  
pp. 1064-1070 ◽  
Author(s):  
Marco Cattaneo ◽  
Alan S Harris ◽  
Ulf Strömberg ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Meta Analysis ◽  
Postoperative Blood Loss ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Transfusion Requirements ◽  
The Mean ◽  
Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

Pharmacokinetics and Tolerability of Factor XIII Concentrates Prepared from Human Placenta or Plasma: a Crossover Randomised Study

1995 ◽  
Vol 74 (02) ◽  
pp. 622-625 ◽  
Author(s):  
H H Brackmann ◽  
R Egbring ◽  
A Ferster ◽  
P Fondu ◽  
J M Girardel ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Bleeding Events ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Randomised Study ◽  
The Mean ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study ◽  
Fxiii Activity ◽  
Observation Period

SummaryThe pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma.Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.

Determination of the Probability Distribution of the Mean Sound Level

2010 ◽  
Vol 35 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Wojciech Batko ◽  
Bartosz Przysucha
Keyword(s):  
Probability Distribution ◽  
Probability Distribution Function ◽  
Mean Value ◽  
Sound Level ◽  
Function Form ◽  
Noise Levels ◽  
Logarithmic Mean ◽  
The Mean ◽  
Estimation Of Uncertainty

AbstractAssessment of several noise indicators are determined by the logarithmic mean <img src="/fulltext-image.asp?format=htmlnonpaginated&src=P42524002G141TV8_html\05_paper.gif" alt=""/>, from the sum of independent random resultsL1;L2; : : : ;Lnof the sound level, being under testing. The estimation of uncertainty of such averaging requires knowledge of probability distribution of the function form of their calculations. The developed solution, leading to the recurrent determination of the probability distribution function for the estimation of the mean value of noise levels and its variance, is shown in this paper.

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