papers Type:Medicine Papers
- Pharmacy Papers
Post Time:2009-8-27 9:58:00
Authors: HUO Qiang ZHANG Zhi-Tao Shi Qing-Ping Xiong JIANG Zhi-wen
[Abstract] Objective To compare the balofloxacin capsules and tablets in healthy human body bioequivalent. Methods 20 healthy volunteers using two-cycle cross-over test, a single oral dose of fasting balofloxacin capsules and tablets of balofloxacin 200mg, HPLC determination of the serum balofloxacin concentration, plasma concentration-time data via DAS2.0 statistical software processing, calculate the main pharmacokinetic parameters, and conduct two kinds of preparations bioequivalence evaluation. Results balofloxacin capsules and tablets balofloxacin main pharmacokinetic parameters were: t1 / 2 (5.666 ± 1.085), and (7.020 ± 2.658) h, cmax (2.912 ± 0.848), and (2.637 ± 0.780) μ g / ml, tmax (1.238 ± 0.631), and (1.400 ± 0.615) h, AUC0 ~ 48 (18.987 ± 4.284), and (20.737 ± 9.681) (μ g * h) / ml. Balofloxacin capsule relative bioavailability (105.30 ± 43.47)%. Conclusion balofloxacin tablets and capsules are bioequivalent.
[Keywords:] balofloxacin tablet; capsules; HPLC; bioequivalence
ABSTRACT Objective To investigate the bioequivalence of balofloxacin capsules and tablets in Chinese healthy volunteers. Methods Twenty volunteers were randomly divided into two groups (test and contral), with double cross over design. The concentration of balofloxacin in serum was determined by HPLC and pharmacokinetic parameters were calculated with DAS2.0 Practical
pharmacokinetics program. Results The pharmaco kinetic parameters of balofloxacin capsules and tablets were as follows: t1 / 2 (5.666 ± 1.085) and (7.020 ± 2.658) h, cmax (2.912 ± 0.848) and (2.637 ± 0.780) μ g / ml, tmax (1.238 ± 0.63) and (1.400 ± 0.615) h, AUC0 ~ 48h (18.987 ± 4.284) and (20.737 ± 9.681) (μ g * h) / ml. The relative bioavalibility of balofloxacin capsules was ( 105.30 ± 43.47)%. Conclusion The result showed that the two preporations of balofloxacin were bioequivalent.
KEY WORDS Balofloxacin capsules; HPLC; Bioequivalence
Received: 2007 04 02 Revised: 2007 08 03
Author: HUO Qiang, male, born in 1974, MA, lecturer. Research direction: drug synthesis and drug dynamics. Balofloxacin (balofloxacin by Japan and South Korea Choongwac Chugai Pharmaceutical joint research and development of new broad-spectrum antibiotic effective . Balofloxacin against Gram-positive bacteria and gram-negative bacteria with broad-spectrum antimicrobial activity, especially for the gold Portuguese bacteria, pneumococcal, enterococci and other Gram-positive bacteria than the activity of norfloxacin, ofloxacin and ciprofloxacin. Balofloxacin has strong bactericidal effect, the MBC and MIC are similar, in in vitro with a longer post-antibiotic effect . balofloxacin selective inhibition of bacterial in vitro antibacterial activity of ciprofloxacin, ofloxacin and lomefloxacin in 4 ~ 16-fold . The Although the use of drugs abroad for many years, but domestic related to the drug pharmacokinetics data not been reported. In this study, 20 healthy volunteers, randomized crossover oral capsules and Balofloxacin Balofloxacin films, interval between doses 1 weeks, both doses of 200mg, high-performance liquid chromatography in human serum Balofloxacin concentration, the concentration of the experiment measured by the DAS 2.0 program fitting processing, for tablets and capsules bioequivalence testing, clinical drug reference. balofloxacin chemical structure shown in Figure 1.
1 Materials and methods
1.1 Drugs and reagents Figure 1 Balofloxacin chemical structure of
Test preparation Balofloxacin capsule, Yingkou AODA Pharmaceutical Co., Ltd., batch number 20,050,203, specifications for each pill is 100mg.
Reference preparation Balofloxacin films, Yingkou AODA Pharmaceutical Co., Ltd., batch number 2.00502 million, specifications for each piece 100mg.
Balofloxacin standard (manufacturer offers, purity 99.0%); lomefloxacin (internal standard), China Pharmaceutical and Biological Products Institution, Lot 0142 9503. Acetonitrile (TEDIA company, chromatographic pure); citric acid (Shanghai Chemical Reagent Company Dong Yi, analytically pure), acetic acid amine (Nanjing Chemical Reagent Factory, analytically pure), trichloroacetic acid (Tianjin big mou chemical equipment supply depot, AR ); self-made multi-distilled water; blank serum (blood banks Bengbu city provided).
1.2 Instrument and HPLC conditions
LC 10Advp high-performance liquid chromatograph, SPD 10Avp UV detector and LC 10ADVP infusion pump for Shimadzu products; N2000 chromatography data Workbench software from Information Engine
ering Co., Ltd., Zhejiang University Zhida production; AT 130 column temperature AUTO Science
box for the company's products; TDZ5 multi-tube rack automatic balancing centrifuge centrifuge equipment by the Xiangjiang Instrument Co., Ltd. production; BT25S electronic balance of Sartorius products. Column: Philo Gate C18 (250mm * 4.6mm, 4μ m), column temperature 40 ℃ ; mobile phase of acetonitrile: 50mmol of citric acid: 1mol/ml acid amine (22:77:1), flow rate 1.0ml/min; detection wavelength 295nm, the sensitivity 0.01AUFS; injection volume 20μ l.
1.3 sample processing [4,5]
Precision drawing Serum 0.5ml, by adding internal standard solution of lomefloxacin (20μ g/ml) 20μ l, scroll 1min; adding 100mg/ml of the trichloroacetic acid extract 0.2ml, vortex 2min, 12000r/min high-speed centrifuge 10min, taking on the clear liquid 20μ l sample.
1.4 Establishment of standard curve of serum
Blank copies of the test tube were added to reference substance solution, dried with nitrogen, then add 0.2ml blank serum to concentrations were 0.1,0.2,0.6,1.0,3.0,4.5 and 6.0μ g/ml, according to sample treatment methods operate under the record balofloxacin and internal standard peak area. To the peak area balofloxacin (Ai) and the internal standard peak area (As) ratio (Ai / As) on the concentration (X, μ g / ml) for linear regression, was the regression equation.
1.5 Determination of precision and recovery
To blank serum preparation of high, medium, low (0.2,1.0, and 4.5μ g/ml) 3 different concentrations balofloxacin standard series, each concentration of five samples for analysis, according to sample processing under the operation of calculating the relative recovery rate, days , day coefficient of variation, evaluation methods precision.
1.6 Subjects Selected
This research program by the National Drug Anhui Province Cancer Hospital Clinical Research Center Medical Ethics
Committee for approval. 20 healthy volunteers, weight (65.1 ± 5.01) kg; age (22.1 ± 1.8) years of age. Were told before the trial may be relevant to all adverse drug reaction, voluntarily signed informed consent. Subjects had no history of drug allergy, no liver, kidney disease, history, mental state good, comprehensive physical examination was normal (including electrocardiogram, heart rate, blood pressure
, liver and kidney functions, chest, urine routine, etc.). Subjects within two weeks before the subjects did not wear any drugs into the test from the beginning until the end of the trial, ban alcohol and any beverage.
1.7 Experimental Design
20 healthy volunteers were randomly divided into two groups of 10 cases, using a single dose of double-cycle randomized crossover trial design, interval of 1 week; per cycle dose of 200mg; medication before the subjects were fasting overnight (10h or more ), at 8 o'clock the next day empty stomach medication, 200ml warm water delivery service, respectively, before treatment (0h), after 0.25,0.5,0.75,1.0,1.5,2.0,3.0,5.0,8.0,12.0,24.0 medication, 36.0 and 48.0h of blood 3ml, set in a test tube, stored at -20 ℃ under test. 2h after medication may be drinking water, 4h unified into the standard diet. In the custody of clinicians to observe the subjects of adverse events. Subjects after taking the drug to avoid the violent activity.
1.8 Data Processing
According to the measured balofloxacin plasma concentration-time data using the DAS 2.0 pharmacokinetic program to calculate balofloxacin reference formulation and testing of preparations the main pharmacokinetic parameters (cmax, tmax with the measured value, AUC calculated using trapezoidal method) and conduct analysis of variance, two-sided t test and (1 ~ 2a) home range analysis, evaluation of two formulations were bioequivalent.
2.1 Method Specificity
This method has good specificity, blank human serum, standard, internal standard and the serum in the detection of drugs within the framework of non-interfering substances, balofloxacin about 10.1min retention time of about an internal standard lomefloxacin retention time of approximately In about 5.4min. Reposted elsewhere in the paper for free download http://eng.hi138.com
2.2 The linear range and the minimum test line
Balofloxacin within the 0.1 ~ 6.0μ g/ml a good linear relationship is expected to be included in the human body Balofloxacin the blood drug concentration, the linear regression equation is:
Y = 0.6184X +0.1709 (n = 7, r = 0.9991)
The lowest detectable concentration in plasma of 0.1μ g/ml (n = 5, RSD% = 13.8).
2.3 The recovery and precision
Serum samples with low, medium, high (0.2,1.0, and 4.5μ g/ml) 3 concentration of days and day RSD were