scholarly journals Bioequivalence Study of Donepezil Hydrochloride Tablets in Healthy Male Volunteers

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Noppamas Rojanasthien ◽  
Siriluk Aunmuang ◽  
Nutthiya Hanprasertpong ◽  
Sukit Roongapinun ◽  
Supanimit Teekachunhatean
Keyword(s):  
High Performance ◽  
Reference Product ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Two Phase ◽  
Test Product ◽  
Male Volunteers ◽  
Bioequivalence Range ◽  
The Mean ◽  
The Difference

The objective of this study was to investigate the bioequivalence of two formulations of 5 mg donepezil HCL tablets: Tonizep as the test and Aricept as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 3-week washout period in 20 healthy Thai Male volunteers. After drug administration, serial blood samples were collected over a period of 216 hours. Plasma donepezil concentrations were measured by high performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0–∞ and were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0–∞ and values of the test product over those of the reference product were 1.08 (1.02–1.14) and 1.08 (0.99–1.17), respectively (within the bioequivalence range of 0.8–1.25). The median for the test product was similar to that of the reference product (2.0 hr), and the 90% CI for the difference between the two preparations was –0.19 to 0.29 hr and within the bioequivalence range of ± 20% of the of the reference formulation. Our study demonstrated the bioequivalence of the two preparations.

scholarly journals Bioequivalence Study of Pantoprazole Sodium-HPBCD and Conventional Pantoprazole Sodium Enteric-Coated Tablet Formulations

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Sandesh P. Kamdi ◽  
Prashant J. Palkar
Keyword(s):  
High Performance ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Two Phase ◽  
Enteric Coated Tablet ◽  
Coated Tablet ◽  
Bioequivalence Range ◽  
The Mean ◽  
Tablet Formulations ◽  
Enteric Coated

The objective of this study was to investigate the bioequivalence of two formulations of 40 mg pantoprazole sodium enteric-coated tablets: Tripepsa as the test and Pantocid as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 1-month washout period in 25 healthy Indian volunteers. After drug administration, serial blood samples were collected over a period of 30 hours. Plasma pantoprazole concentrations were measured by high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of and were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of and values of the test product over those of the reference product were 90.21 (83.69–97.24) and 108.68 (100.21–117.86), respectively (within the bioequivalence range of 80–125%). On the basis of pharmacokinetic parameters including , , and values, both the formulations were bioequivalent.

scholarly journals The Statistical Analysis of Pharmacokinetic Parameters in the Context of Bioequivalence Testing of Two Anthelmintic Formulas Based on Ivermectine and Triclabendazole in Sheep

2019 ◽  
Vol 65 (2) ◽  
pp. 60-65
Author(s):  
Lenard Farczadi ◽  
Laurian Vlase ◽  
Orsolya Melles ◽  
Ramona Tolomeiu ◽  
Octavia Tamas-Krumpe ◽  
...  
Keyword(s):  
High Performance ◽  
Reference Product ◽  
Plasma Concentrations ◽  
Pharmaceutical Formulations ◽  
Relative Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Test Product

AbstractConducting bioequivalence studies is an essential step during the market authorization process of generic pharmaceutical formulations, for both human or veterinary use. The aim of the present study was to evaluate the pharmacokinetics of triclabendazole sulphoxide, the main metabolite of triclabendazole, and ivermectin in order to evaluate the bioavailability and bioequivalence of a novel sheep anthelmintic formulation of oral suspension for sheep treatment containing triclabendazole 50 mg/mL and ivermectin 1 mg/mL compared to the reference product. In order to determine relative bioavailability of the test product with respect to the reference product the study was conducted on 36 clinically healthy sheep, following an unicentric, randomized, cross-over, two-sequence, two-treatment and 14-day wash-out study design. For the determination of triclabendazole sulphoxide and ivermectin sheep plasma concentrations, two rapid, selective high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) methods were developed and validated. The measured plasma concentrations of triclabendazole sulphoxide and ivermectin were used for the pharmacokinetic analysis and the determination of bioequivalence between the test product with regards to the reference product. The noncompartmental analysis of the pharmacokinetic data for both triclabendazole sulphoxide and ivermectin showed similarities between first-order kinetics of the test and reference product. The relevant pharmacokinetic parameters (Cmax, AUClast, AUCtot) were determined and the bioequivalence between the test and reference product could be concluded.

scholarly journals BIOEQUIVALENCE STUDY OF AZELNIDIPINE 16 MG TABLET TO EVALUATE PHARMACOKINETIC PROFILE OF SINGLE DOSE IN HEALTHY, ADULT, HUMAN VOLUNTEERS UNDER FASTING CONDITION

2021 ◽  
pp. 154-159
Author(s):  
DIBYA DAS ◽  
DHIMAN HALDER ◽  
ANIRBANDEEP BOSE ◽  
CHIRANJIT SAHA ◽  
HIMANGSHU SEKHAR MAJI ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Plasma Sample ◽  
Reference Product ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Entire Study ◽  
Test Product ◽  
Fasting Condition

Objective: The present study's objective is to conduct a comparative bioavailability study with a special emphasis on the test product's bioequivalence using a standard reference product as a comparator. Methods: Before initiating the bioequivalent study, the plasma sample analysis method was developed and validated by using LC-MS/MS method. The entire study was conducted as a single-dose crossover randomized bioequivalence study with open-label, two treatment, two-period, and two sequences on 24 healthy volunteers under fasting condition. With proper informed consent process the oral dose of the Reference product (R) or Test product (T) was administered on healthy volunteers at 0 h during each period of the study. After the drug's oral administration, a certain quantity of blood sample was collected, and the plasma sample was separated using a cold centrifuge. The plasma samples were analysed by using the validated LC-MS/MS method. The pharmacokinetic parameters, statistical data and ANOVA of the test and reference product were evaluated. Results: The Cmax, Auc0-t, AUC0-∞ and tmax of the test product were found to be 6.29 ng/ml, 117.0 ng. h/ml, 161.67 ng. h/ml and 3.33 h. respectively. And the Cmax, Auc0-t, AUC0-∞ and tmax of reference product were found 6.59 ng/ml, 123.21 ng. h./ml, 172.20 ng. h/ml and 3.38 h respectively. Relative bioavailability was found 94.96%. The overall results show that the 90% confidence intervals (Log-Transformed and Untransformed) for Cmax, AUC0-t and AUC0-∞ for Azelnidipine were within the acceptable limit of 80%-125%. Conclusion: The entire study's conclusion can be drawn as the test product was bioequivalent with the reference product's comparator.

scholarly journals Phenylalanine requirement in children with classical PKU determined by indicator amino acid oxidation

2002 ◽  
Vol 283 (6) ◽  
pp. E1249-E1256 ◽  
Author(s):  
Glenda Courtney-Martin ◽  
Rachelle Bross ◽  
Mahroukh Raffi ◽  
Joe T. R. Clarke ◽  
Ronald O. Ball ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Oxidation ◽  
Phenylalanine Concentration ◽  
Two Phase ◽  
Amino Acid Oxidation ◽  
Blood Phenylalanine ◽  
Plasma Phenylalanine ◽  
Crossover Analysis ◽  
The Mean ◽  
The Difference

Dietary restriction of phenylalanine is the main treatment for phenylketonuria (PKU), and current estimates of requirements are based on plasma phenylalanine concentration and growth. The present study aimed to determine more precisely the phenylalanine requirements in patients with the disease by use of indicator amino acid oxidation, withl-[1-13C]lysine as the indicator. Breath13CO2 production (F13 co 2) was used as the end point. Finger-prick blood samples were also collected for measurement of phenylalanine to relate phenylalanine intake to blood phenylalanine levels. The mean phenylalanine requirement, estimated using a two-phase linear regression crossover analysis, was 14 mg · kg−1 · day−1, and the safe population intake (upper 95% confidence interval of the mean) was found to be 19.5 mg · kg−1 · day−1. A balance between phenylalanine intake and the difference between fed and fasted blood phenylalanine concentration was observed at an intake of 20 mg · kg−1 · day−1. The similarity between these two values (19.5 and 20 mg · kg−1 · day−1) suggests that the maximal phenylalanine intake for children with PKU should be no higher than 20 mg · kg−1 · day−1.

scholarly journals A sensitive and reliable RP-HPLC method for the detection of cimetidine – a H2 receptor antagonist in human plasma

2019 ◽  
Vol 8 (3) ◽  
pp. 671-674
Keyword(s):  
Human Plasma ◽  
High Performance ◽  
Internal Standard ◽  
Bioequivalence Study ◽  
High Concentration ◽  
H2 Receptor Antagonist ◽  
Chromatography Method ◽  
Thaw Cycle ◽  
Limit Of Quantitation ◽  
The Mean

Bioanalytical methods for bioequivalence studies require high sensibility and rapidity due to the large number of samples and the low plasma concentration of drugs. The present study aimed to develop and validate a high-performance liquid chromatography method to quantify cimetidine (CMT) in human plasma and to apply it in a bioequivalence study. Spiked plasma of 500 µl (l, m and h concentration) was used for the assay. The HPLC injection volume was 20μl of the reconstitute sample where, 2 ml of ethyl acetate used for extraction purposes. Cimetidine was prepared separately for low (80 ng/ml), medium (2000 ng/ml) and high (3600 ng/ml) concentrations and internal standard (ranitidine) concentration was 3000 ng/ml. Freeze thawing and long terms stability were conducted at -25º c. The individual calibration curve for spiked standards was linear with R2= 0.99. The inaccuracy values for QC samples were within 15% of the actual value and not more than 20% for the LOQ. The limit of quantitation (LOQ) was 40 ng/ml, which was also the lowest concentration of cimetidine that was quantitated with the variability of 5.9%. The within day precision and between day precision for LOQ were 10.8 and 5.9 respectively. The retention time for the analyte was 4.1-4.5 minutes during the within a day and between day results. The mean % inaccuracy values for low, medium and high concentration were 6.8, 5.6 and 7.8 respectively for within day and 2.4, 6.1 and 7.9 respectively for between days. The within day and between day % inaccuracy for LOQ concentration was 12.4 and 5.5 respectively. The mean recoveries for low, medium and high concentration of cimetidine were 80.2, 70.9 and 74.2. The overall mean recovery for cimetidine was 75.1%. The maximum inaccuracy for freeze thaw cycle and long term stability samples for low, medium and high was found with CV less than 15% for all concentrations, indicating that cimetidine is stable. The developed method was precise and accurate and was suitable to be applied for the bioequivalence study of cimetidine.

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

Pharmacokinetics of Prilocaine after Intravenous Administration in Volunteers 

1999 ◽  
Vol 90 (4) ◽  
pp. 988-992 ◽  
Author(s):  
Auke Dirk van der Meer ◽  
Anton G. L. Burm ◽  
Rudolf Stienstra ◽  
Jack W. van Kleef ◽  
Arie A. Vletter ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Equilibrium Dialysis ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Unbound Fraction ◽  
Blood Samples ◽  
The Mean ◽  
The Difference

Background Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate. Methods Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis. Results The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P < 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P < 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P < 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P < 0.005). Conclusions The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.

scholarly journals Analysis of incapacitation during +Gz induced loss of consciousness

2021 ◽  
Vol 65 ◽  
pp. 91-96
Author(s):  
MD Sharma ◽  
P Biswal ◽  
N Taneja ◽  
A Agarwal
Keyword(s):  
Air Force ◽  
High Performance ◽  
Age Groups ◽  
Rapid Onset ◽  
Loss Of Consciousness ◽  
Video Recordings ◽  
Operational Capabilities ◽  
Significant Difference ◽  
The Mean ◽  
The Difference

Introduction: Occurrence of G induced loss of consciousness (G-LOC) during centrifuge training is a known entity. The Indian Air Force is currently undertaking high G training of its fighter pilots in High Performance Human Centrifuge (HPHC) which has significantly higher operational capabilities. The study aimed to analyse the incapacitation periods and myoclonic jerks associated with G-LOC occurring during HPHC training. Material and Methods: Records of episodes of 161 G-LOC during closed loop Rapid Onset Rates (ROR) runs over a period of 7 years from 2011 to 2017 were analyzed. The video recordings of these G-LOC episodes were assessed in terms of the participant demographics, +Gz onset rates, incapacitation periods, and presence or absence of myoclonic jerks during the G-LOC episodes. Descriptive statistics was applied to analyze the incapacitation periods and the duration of the myoclonic flail movements. Single tailed t-test was used to analyze the difference between the incapacitation periods of the aircrew who suffered myoclonic flail movements and those who did not. One-way ANOVA was carried out to assess the differences in incapacitation periods, if any, between aircrew of different age groups. Significance was set at P < 0.05. Results: Of these 161 episodes of G-LOC, 43.5% were seen in trainee aircrew. The mean Absolute Incapacitation Period (AIP), Relative Incapacitation Period (RIP) and Total Incapacitation Period (TIP) was 6.9 ± 2.3 s, 12.2 ± 4.7 s, and 19.1 ± 5.5 respectively. Age and flying experience did not show any significant effect with any of the incapacitation periods (p>0.05). The TIP correlated better with the RIP than with the AIP (Pearson’s correlation values of 0.9 and 0.52 respectively). Myoclonic flail movements were witnessed in 25.5% of G-LOC episodes with an average duration of 5.3 s and more than 50% occurring at ≥8Gz. The mean duration of RIP was significantly higher (P=0.03) when G-LOC was associated with myoclonic flail movements, whereas, the duration of AIP did not show any significant difference. Conclusion: The shorter incapacitation periods observed in the study compared to that reported in most of the previous studies could be attributed to the faster Gz offset rates of the present HPHC. Episodes of G-LOC having myoclonic movements were found to have higher relative incapacitation periods. Even though these movements were associated with G-LOC occurring at higher Gz levels, the durations were independent of the Gz levels.

scholarly journals Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

2020 ◽  
Author(s):  
Li Xin ◽  
Chenjing Wang ◽  
Ting Li ◽  
Yanping Liu ◽  
Shuqin Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
Healthy Chinese ◽  
Chinese Subjects

Abstract Background: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.Results: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80~125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70±0.49) ng/mL, AUC0-t was (141.32±36.24) ng×h/mL and AUC0-∞ was (157.14±45.65) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83±0.52) ng/mL, AUC0-t was (153.62±33.96) ng×h/mL and AUC0-∞ was (173.05±41.78) ng×h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73±0.55) ng/mL, AUC0-t was (166.93±49.96) ng×h/mL and AUC0-∞ was (190.99±70.89) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87±0.81) ng/mL AUC0-t was (165.46±43.58) ng×h/mL and AUC0-∞ was (189.51±64.70) ng×h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.Conclusion: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

scholarly journals Induction of theophylline clearance by rifampin and rifabutin in healthy male volunteers.

1996 ◽  
Vol 40 (8) ◽  
pp. 1866-1869 ◽  
Author(s):  
J G Gillum ◽  
J M Sesler ◽  
V L Bruzzese ◽  
D S Israel ◽  
R E Polk
Keyword(s):  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Theophylline Clearance ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Male Volunteers ◽  
Hepatic Microsomal Enzyme ◽  
The Mean ◽  
To Receive

Rifampin and rifabutin induce the metabolism of many drugs, which may result in subtherapeutic concentrations and failure of therapy. However, differences between rifabutin and rifampin in potency of induction, and the specific enzymes which are altered, are not clear. This study, involving 12 adult male volunteers, compared the effects of 14-day courses of rifampin and rifabutin on clearance of theophylline, a substrate for the hepatic microsomal enzyme CYP1A2. Subjects were given oral theophylline solution (5 mg/kg of body weight) on day 1 and then randomized to receive daily rifampin (300 mg) or rifabutin (300 mg) on days 3 to 16. Theophylline was readministered as described above on day 15. The first treatment sequence was followed by a 2-week washout period; subjects then received the alternative treatment. Theophylline concentrations were determined for 46 h after each dose, and pharmacokinetic parameters were determined. One subject developed flu-like symptoms while taking rifabutin and withdrew voluntarily. Results from the remaining 11 subjects are reported. Compared with the baseline, the mean area under the concentration-time curve (AUC) (+/- standard deviation) for theophylline declined significantly following rifampin treatment (from 140 +/- 37 to 100 +/- 24 micrograms . h/ml, P <0.001); there was no significant change following rifabutin treatment (136 +/- 48 to 128 +/- 45 micrograms.h/ml). Baseline theophylline AUCs before each treatment phase were not different. A comparison of equal doses of rifampin and rifabutin administered to healthy volunteers for 2 weeks indicates that induction of CYP1A2, as measured by theophylline clearance, is significantly less following rifabutin treatment than it is following rifampin treatment. However, the relative induction potency for other metabolic enzymes remains to be investigated.

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