Bioavailability and efficacy characteristics of two different oral liquid formulations of albendazole

The oral bioavailability and anthelmintic efficacy in mice of a new formulation of albendazole (ABZ) dissolved in a solution of hydroxypropyl-β-cyclodextrin (HPCD) are compared with a conventional ABZ suspension of carboxymethylcellulose. Plasma concentrations of ABZ and albendazole sulphoxide (ABZ-SO), its active and main metabolite, were assayed by HPLC. The AUC_0–∞ and C_max values obtained for both ABZ and ABZ-SO, after administration of the ABZ–HPCD solution were significantly higher (P<0.01) than those obtained from the ABZ suspension. Although, the differences between the ABZ and ABZ-SO-T_max values were found not to be significant, regardless of the formulation. The anthelmintic activities against enteral (pre-adult) and parenteral (migrating and encysted larvae) stages of Trichinella spiralis were studied in mice. The ABZ solution was more efficient against pre-adult and encysted larvae than the ABZ suspension. The efficacy differences between both formulations against the migrating larvae, were found to be not significant (P<0.05). For the migrating parasite stage, there was a linear correlation between the anthelmintic activity and pharmacokinetical parameters with respect to the ABZ-AUC_0–∞ value. Meanwhile, for the muscular encysted parasite stage, better relationships were obtained for AUC_0–∞ and C_max values from ABZ-SO, which had correlation coefficients of 0.996 and 0.987, respectively.     

The application of partial areas in assessment of rate and extent of absorption in bioequivalence studies of conventional release products: experimental evidence

A bioequivalence study on perphenazine/amitriptyline combination compared three formulations (TST-1, TST-2 and REF) containing the same nominal dose of perphenazine, while TST-2 contained 20% less amitriptyline than the other two formulations. ANOVA-SNK on log-transformed partial areas AUC₀²⁴ through AUC₀^∞ showed the intra-subject variabilities of perphenazine to be consistently higher than those of amitriptyline or nortriptyline. There was also a marked increase in intra-subject variability for perphenazine on extrapolating AUC₀^last to infinity. Thus, whhile the 1–2 confidence intervals (90% CIs) and ratios of geometric means for perphenazine fell within preset limits of 80–125% in all pairwise comparisons, the CIs for AUC₀^∞ violated the upper limit in comparisons of TST-2 and REF (or TST-2 and TST-1). This outcome could be attributed to high intra-subject variability on AUC₀^∞. ANOVA-SNK of amitriptyline identified a significant difference in extent of amitriptyline absorbed from TST-2 compared with TST-1 and REF. Thus, in pairwise comparisons between TST-1 and REF, all 90% CIs for amitriptyline partial areas AUC₀⁴ through AUC₀^∞ fell within 80–125% limits. In corresponding comparisons between TST-2 and REF (or TST-2 and TST-1), however, the lower limit of the 90% CIs for AUC₀¹ through AUC₀^last consistently fell below the 80% cut off. By contrast, 90% CIs associated with the ratios C_max/AUC₀⁴ through C_max/AUC₀^∞ all fell within preset limits indicating no differences in absorption rate of amitriptyline, consistent with the theoretical argument that C_max/AUC is influenced by rate but not extent of absorption. Thus the partial area method is applicable to the evaluation of both relative rate and extent of absorption from conventional release products. Similarly, analyses of nortriptyline data showed that the partial area method is also effective in the evaluation of rate and extent of formation of a metabolite in a bioequivalence study. The partial area method permits a greater number of plasma samples to be devoted to accurate estimation of t_max and C_max since the necessity to estimate AUC₀^∞ is obviated.     

Evaluation of microcrystalline chitosans for gastro-retentive drug delivery

In vivo absorption studies were carried out in human volunteers to evaluate whether microcrystalline chitosan (MCCh) granules would be gastro-retentive. Furosemide, which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. The rate of release of furosemide in vitro could be prolonged by increasing the molecular weight (M_w) or amount of MCCh (150 to 240 kDa; 80 to 95%) in the granules, and also by addition of acidic excipients to the formulations. No marked changes in the in vivo absorption rate (t_max) were noted, but the amounts of furosemide absorbed (AUC_0–∞ and C_max) decreased as the in vitro release rate decreased, although this was not statistically significant in the case of AUC. The highest AUC_0–∞ (3050 μg l⁻¹ h) for furosemide (40 mg) was achieved with granules containing 80% MCCh of 150 kDa M_w. With MCCh of 240 kDa M_w AUC_0–∞ was 1890 μg l⁻¹ h. This kind of pharmacokinetic profile of furosemide suggests that the gastric retention time of the granules is too short in relation to the release rate, and a large amount of the drug passes its “absorption window” before being released. The in vivo study produced no evidence that the chitosan formulations studied can be used as mucoadhesive gastro-retentive drug delivery systems. The results of in vitro mucoadhesion studies did not predict the results of in vivo studies.     

Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica

This study aims to evaluate the in vivo performance of ordered mesoporous silica (OMS) as a carrier for poorly water soluble drugs. Itraconazole was selected as model compound. Physicochemical characterization was carried out by SEM, TEM, nitrogen adsorption, DSC, TGA and in vitro dissolution. After loading itraconazole into OMS, its oral bioavailability was compared with the crystalline drug and the marketed product Sporanox^® in rabbits and dogs. Plasma concentrations of itraconazole and OH–itraconazole were determined by HPLC-UV. After administration of crystalline itraconazole in dogs (20 mg), no systemic itraconazole could be detected. Using OMS as a carrier, the AUC_0–8 was boosted to 681 ± 566 nM h. In rabbits, the AUC_0–24 increased significantly from 521 ± 159 nM h after oral administration of crystalline itraconazole (8 mg) to 1069 ± 278 nM h when this dose was loaded into OMS. T_max decreased from 9.8 ± 1.8 to 4.2 ± 1.8 h. No significant differences (AUC, C_max, and T_max) could be determined when comparing OMS with Sporanox^® in both species. The oral bioavailability of itraconazole formulated with OMS as a carrier compares well with the marketed product Sporanox^®, in rabbits as well as in dogs. OMS can therefore be considered as a promising carrier to achieve enhanced oral bioavailability for drugs with extremely low water solubility.     

HPLC determination of anethole trithione and its application to pharmacokinetics in rabbits

To evaluate the relative bioavailability of anethole trithione (ATT) from self-microemulsifying drug delivery system (SMEDDS) and tablet, a sensitive, accurate and reliable liquid chromatography method was developed and validated to determine ATT in rabbit plasma. Chromatographic separation was performed on a Diamonsil C₁₈ column by using a mixture of methanol–water (90:10, v/v) delivered at a flow rate of 1.0 ml/min. The wavelength was set at 348 nm and mifepristone was used as the internal standard. A linear relationship for ATT was found in the range of 0.5–32 ng/ml. The mean extraction recoveries of ATT determined over three concentrations were 84.7 ± 5.8, 92.3 ± 3.4 and 89.9 ± 5.1%. After administration of SMEDDS and tablets to rabbits, significant differences were found in main pharmacokinetic parameters of T_max, C_max and AUC_0–∞ between these two formulations, and a 2.5-fold enhancement of relative bioavailability of ATT was observed from the SMEDDS compared with tablets.     

Intrapulmonary pharmacokinetics and pharmacodynamics of meropenem

The objective of this study was to determine the plasma and intrapulmonary pharmacokinetic parameters of intravenously administered meropenem in healthy volunteers. Four doses of 0.5 g, 1.0 g or 2.0 g meropenem were administered intravenously to 20, 20 and 8 healthy adult subjects, respectively. Standardised bronchoscopy and timed bronchoalveolar lavage (BAL) were performed following administration of the last dose. Blood was obtained for drug assay prior to drug administration and at the time of BAL. Meropenem was measured in plasma, BAL fluid and alveolar cells (ACs) using a combined high pressure liquid chromatographic–mass spectrometric technique. Plasma, epithelial lining fluid (ELF) and AC pharmacokinetics were derived using non-compartmental methods. C_max/MIC₉₀ (where C_max is the maximum plasma concentration and MIC₉₀ is the minimum inhibitory concentration required to inhibit 90% of the pathogen), AUC/MIC₉₀ (where AUC is the area under the curve for the mean concentration–time data), intrapulmonary drug exposure ratios and percent time above MIC₉₀ during the dosing interval (%T > MIC₉₀) were calculated for common respiratory pathogens with MIC₉₀ values of 0.12–4 μg/mL. In the 0.5 g dose group, the C_max (mean ± S.D.), AUC_0–8 h and half-life for plasma were, respectively, 25.8 ± 5.8 μg/mL, 28.57 μg h/mL and 0.77 h; for ELF the values were 5.3 ± 2.5 μg/mL, 12.27 μg h/mL and 1.51 h; and for ACs the values were 1.0 ± 0.5 μg/mL, 4.30 μg h/mL and 2.61 h. In the 1.0 g dose group, the C_max, AUC_0–8 h and half-life for plasma were, respectively, 53.5 ± 19.7 μg/mL, 55.49 μg h/mL and 1.31 h; for ELF the values were 7.7 ± 3.1 μg/mL, 15.34 μg h/mL and 0.95 h; and for ACs the values were 5.0 ± 3.4 μg/mL, 14.07 μg h/mL and 2.17 h. In the 2.0 g dose group, the C_max, AUC_0–8 h and half-life for plasma were, respectively 131.7 ± 18.2 μg/mL, 156.7 μg h/mL and 0.89 h. The time above MIC in plasma ranged between 28% and 78% for the 0.5 g dose and between 45% and 100% for the 1.0 g and 2.0 g doses. In ELF, the time above MIC ranged from 18% to 100% for the 0.5 g dose and from 25% to 88% for the 1.0 g dose. In ACs, the time above MIC ranged from 0% to 100% for the 0.5 g dose and from 24% to 100% for the 1.0 g dose. Time above MIC in ELF and ACs for the 2.0 g dose was not calculated because of sample degradation. The prolonged T > MIC₉₀ and high intrapulmonary drug concentrations following every 8 h administration of 0.5–2.0 g doses of meropenem are favourable for the treatment of common respiratory pathogens.     

Efficacy and pharmacodynamics of gemifloxacin versus levofloxacin in guinea pig pneumococcal pneumonia induced by strains with decreased ciprofloxacin susceptibility

Quinolone in vivo bactericidal activity was investigated in a guinea pig pneumonia model using three Streptococcus pneumoniae strains with decreasing susceptibility to ciprofloxacin. Treatment regimens resulted in values of AUC_{0–24 h} and C_{30 min} similar to those of standard oral regimens in human serum. Efficacy was defined as a significant difference in number of viable bacteria in the lungs compared with the control. Ciprofloxacin, levofloxacin and gemifloxacin were effective against the levofloxacin-susceptible strain. Only gemifloxacin achieved a ≥99.9% reduction versus control against the levofloxacin intermediate-resistant strain. Gemifloxacin achieved a 99.69% reduction and was the only quinolone significantly different from the control (P<0.05) against the levofloxacin-resistant strain. Gemifloxacin offers in vivo activity against ciprofloxacin- to levofloxacin-resistant pneumococci.     

In vivo pharmacokinetics in human volunteers: oral administered guar gum-based colon-targeted 5-fluorouracil tablets

The objective of the present study is to compare the guar gum-based colon-targeted tablets of 5-fluorouracil against an immediate release tablet by in vitro dissolution and in vivo pharmacokinetic studies in human volunteers. Twelve healthy volunteers participated in the study. 5-Fluorouracil was administered at a dose of 50 mg both in immediate release tablet and colon-targeted tablet. On oral administration of colon-targeted tablets, 5-fluorouracil started appearing in the plasma at 6 h, and reached the peak concentration (C_max of 216±15 ng/ml) at 7.6±0.1 h (T_max), whereas the immediate release tablets produced peak plasma concentration (C_max of 278±21 ng/ml) at 0.6±0.01 h (T_max). The AUC_0−∞ for 5-fluorouracil from colon-targeted tablet and immediate release tablet were found to be 617±39 and 205±21 ng/ml/h, respectively. Colon-targeted tablets showed delayed t_max, delayed absorption time (t_a), decreased C_max and decreased absorption rate constant when compared to the immediate release tablets.The results of the study indicated that the guar gum-based colon-targeted formulation did not release the drug in stomach and small intestine, but delivered it to the colon resulting in a slow absorption of the drug and making it available for local action in colon.     

Evaluation of gatifloxacin pharmacokinetics and pharmacodynamics in severely ill adults in a medical Intensive Care Unit

A prospective, open-label study investigated the steady-state pharmacokinetics of gatifloxacin in 20 adult patients in a medical Intensive Care Unit (ICU). Twelve patients had normal or moderately impaired renal function (creatinine clearance (CrCL) ≥40 mL/min) and received gatifloxacin 400 mg intravenously once daily. Eight patients had CrCL < 40 mL/min and received 200 mg doses. Gatifloxacin plasma and urine concentrations were determined by validated high-performance liquid chromatography. Mean ± standard deviation gatifloxacin elimination half-life (t_1/2), systemic clearance and volume of distribution in patients with CrCL ≥ 40 mL/min were 10.8 ± 1.5 h, 156 ± 29 mL/min and 1.8 ± 0.2 L/kg, respectively. Maximum and minimum serum concentrations (C_max and C_min) and area under the serum concentration–time curve from 0–24 h (AUC_0–24) in these patients were 4.77 ± 0.76 mg/L, 1.08 ± 0.28 mg/L and 44.4 ± 9.2 mg h/L, respectively. Observed t_1/2, C_max and AUC_0–24 following 200 mg doses in patients with poor renal function (CrCL < 40 mL/min) were 18.2 ± 3.3 h, 2.85 ± 0.76 mg/L and 36.6 ± 3.4 mg h/L, respectively. Statistically significant (P < 0.05) increase in AUC_0–24 and decreases in t_1/2 and clearance (total and renal) were observed in ICU patients administered intravenous gatifloxacin compared with previous data in healthy volunteers. Pharmacodynamic evaluation by Monte Carlo simulation indicated that approved gatifloxacin dosage regimens appear to be adequate for most pathogens (minimum inhibitory concentration (MIC) ≤0.5 μg/mL) associated with community-acquired infections in severely ill ICU patients; less susceptible pathogens (MIC ≥ 1 μg/mL) do not appear to be optimally treated with currently approved doses.     

Pharmacokinetic evaluation of an azithromycin controlled release dosage form in healthy human volunteers: a single dose study

Azithromycin (AZI) follows a two-compartment model pharmacokinetically. The purpose of this study was to evaluate the in vivo performance of a controlled release (CR) formulation of AZI, which would eliminate the risk of high peak plasma concentrations obtained within 2–3 h after peroral administration of immediate release (IR) products. The study was conducted in twelve healthy male human volunteers to compare an experimental NIPER product (CR tablets) with Vicon^® (IR tablets) at the same dose level as a single-dose, randomized, one-period, two-treatment, and parallel-study. Concentrations of AZI in serum samples were assessed using the validated HPLC method. From the serum concentration–time profiles various pharmacokinetic parameters (AUC_0–96, AUC_0–inf, C_max and T_max) were calculated for both products. Results showed that the high peak concentration obtained by administration of a conventional IR formulation were eliminated with the CR product. A mean dosage form index (DI) of 1.17 with fluctuations of 7.57% was obtained with the CR product at steady state level, indicating reduced fluctuations at the steady state serum concentrations. Elimination of the pronounced peak as well as fluctuations reduced or minimized AZI adverse effects associated with the IR product.     

酮洛芬择时释药片Beagle犬体内的生物等效性

目的：研究酮洛芬择时释药片（受试制剂）和酮洛芬胶囊（参比制剂）在Beagle犬体内的药动学特征和生物等效性。方法：采用双周期双交叉试验，每只Beagle犬口服受试制剂和参比制剂，于相应时间点取静脉血检测酮洛芬血药浓度。采用DAS 2.1.1软件分别计算2种制剂的药动学参数，并计算受试制剂的相对生物利用度。通过统计学分析比较2种制剂的生物等效性。结果：受试制剂和参比制剂的主要药动学参数分别为t_1/2（4.28±1.59）h和（5.90±2.33）h，C_max（61.36±2.37）μg·mL^-1和（67.59±10.72）μg·mL^-1，t_max（5.83±0.61）h和（2.04±0.19）h，t_lag（3.46±0.25）h和（0.46±0.22）h，AUC_0-t（341.16±19.09）μg·h·mL^-1和（355.93±51.82）μg·h·mL^-1，AUC_0-∞（354.29±19.91）μg·h·mL^-1和（416.77±42.49）μg·h·mL^-1，受试制剂的相对生物利用度为85.01%。结论：受试制剂和参比制剂的AUC_0-t、C_max是生物等效性的，但在t_max、t_lag生物不等效。受试制剂在一定的时滞（约3.458h）后释药，符合择时释药制剂的释药要求。     

Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion

To improve the bioavailability and photostability of poorly water-soluble and photosensitive amlodipine, dry emulsion (DE) was prepared by spray-drying the oil-in-water emulsion of amlodipine. Labrafil M 1944 CS and dextrin were employed as oil phase and matrix material, respectively. Dispersing DE in distilled water formed an emulsion with a mean droplet size 1.4-fold larger than that of the homogenized amlodipine emulsion before spray-drying (0.24 ± 0.30 μm versus 0.17 ± 0.02 μm). The mean droplet size of DE remained unchanged during 6-month storage at room temperature. 94.4% versus 33.1% of amlodipine remained intact after 24-h UV irradiation of amlodipine as DE formulation or as powder. These data suggest that DE formulation greatly improved the photostability of amlodipine, as well as increasing the physical stability of emulsion systems. In vitro release of DE was higher than that of amlodipine powder (66% versus 48% release at 60 min). Consequently, DE formulation resulted in 2.6- and 2.9-fold higher C_max and AUC_0–24 h of amlodipine compared after oral administration of amlodipine powder in rats. Our data suggest that the DE may be a potential oral dosage form for amlodipine to improve its bioavailability.     

硫酸沙丁胺醇吸入气雾剂药动学等效性评价技术与流程研究

目的： 建立硫酸沙丁胺醇吸入气雾剂药动学等效性评价技术与流程。方法： 6名健康受试者双周期空腹经口吸入硫酸沙丁胺醇吸入气雾剂200 μg（2掀）,2周期间清洗期为7 d。采用超高效液相色谱-质谱联用法测定人血浆中沙丁胺醇浓度。DAS 3.2.8软件统计血药浓度-时间数据。计算药动学参数C_max、AUC_{0-20 min}、AUC_0-t和AUC_0-∞及其个体内变异系数。结果： 硫酸沙丁胺醇吸入气雾剂第一周期和第二周期的主要药动学参数C_max分别为（285.33±158.83）pg·mL^-1和（222.12±108.02）pg·mL^-1,t_max分别为（0.72±0.52）h和（1.03±1.03）h,t_1/2z分别为（6.39±1.75）h和（5.91±1.22）h,AUC_{0-20 min}分别为（63.77±42.27）pg·h·mL^-1和（47.56±33.54）pg·h·mL^-1,AUC_0-t分别为（1 469.79±701.96）pg·h·mL^-1和（1 292.24±498.59）pg·h·mL^-1,AUC_0-∞分别为（1 596.30±772.95）pg·h·mL^-1和（1 383.21±488.82）pg·h·mL^-1。药动学参数C_max、AUC_{0-20 min}、AUC_0-t和AUC_0-∞的个体内变异系数分别为29.04%、17.64%、27.12%和27.63%。结论： 本研究建立了一种简便、经济和准确的硫酸沙丁胺醇吸入气雾剂药动学等效性评价技术与流程。     

High-performance liquid chromatographic method for the bioequivalence evaluation of desloratadine fumarate tablets in dogs

A simple HPLC method was developed for the determination of desloratadine in dog plasma and was used for evaluating the bioequivalence of desloratadine fumarate tablets and desloratadine tablets in dogs. Chromatographic separation was performed on a Hypersil CN column (150 mm×5.0 mm, 5 μm) using a mixture of methanol, acetonitrile and phosphate buffer (pH 5.5; 0.01 mol/l) (35:35:30, v/v/v) as mobile phase delivered at a flow rate of 0.8 ml/min. The detection was set at 241 nm. The limit of quantitation was 5.0 ng/ml. The calibration range was from 5.0 to 800.0 ng/ml. Inter- and intra-day precision ranged from 1.8 to 3.8% and from 2.2 to 9.0%, respectively. The recovery of desloratadine from dog plasma ranged from 78.8 to 82.0%. The developed method was applied to the bioequivalence studies of desloratadine fumarate tablets (test preparation) and desloratadine tablets (reference preparation) in five dogs. Pharmacokinetic parameters t_max, C_max, AUC_0–t, AUC_0–∞, t_1/2 were determined from plasma concentration-time profiles of both preparations. The analysis of variance (ANOVA) did not show any significant difference between the two preparations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two preparations exhibited comparable pharmacokinetic profiles and that desloratadine fumarate tablets was bioequivalent to desloratadine tablets.     

Evaluation of different partial AUCs as indirect measures of rate of drug absorption in comparative pharmacokinetic studies

The performance of different partial AUCs, including partial AUC from zero to t_max of the reference formulation (AUC_r) and partial AUC from zero to t_max of test or reference formulation, whichever occurs earliest (AUC_e), as indirect measures of rate of absorption have been evaluated using simulated experiments. The performance of these metrics relative to C_max, t_max and C_max/AUC_∞ was further assessed using the results of actual studies involving a Glaxo drug. The normalised metrics AUC_r/AUC_∞ and AUC_e/AUC_∞ have also been evaluated. Our provisional conclusions were: (1) AUC_r/AUC_∞ and AUC_e/AUC_∞ had greater statistical power than C_max and the non-normalised partial AUCs at detecting true differences in rate of absorption. Using real data, the performance of AUC_e/AUC_∞ was poor, however, the performance of AUC_r/AUC_∞ was good; (2) C_max/AUC_∞ was more precisely estimated than AUC_r/AUC_∞ or AUC_e/AUC_∞ and may be a superior metric for assessing absorption rates of highly variable drugs.     

Enhanced nasal absorption of hydrophilic markers after dosing with AT1002, a tight junction modulator

AT1002 is a six-mer synthetic peptide, H-FCIGRL-OH, that retains the delta G and Zot biological activity of reversibly opening tight junctions and increases the paracellular transport of drugs. The objective of this study was to evaluate the possible use of AT1002 in enhancing the nasal availability of macromolecules using large paracellular markers as model agents. Male Sprague–Dawley rats cannulated in the jugular vein were randomly assigned to receive radiolabelled paracellular markers, [¹⁴C]PEG4000 or [¹⁴C]inulin, with/without AT1002, for each intranasal study. The plasma concentration of PEG4000 with AT1002 (10 mg/kg) was significantly higher than that from PEG4000 control over 360 min following intranasal administration. The AUC_0–360 min and C_max from the PEG4000/AT1002 (10 mg/kg) treatment were statistically (p < 0.05) increased to 235% and 357%, of control, respectively. When inulin was administered with AT1002 (10 mg/kg), the plasma concentration was significantly higher (p < 0.05) than control over 360 min, and increases (p < 0.05) of 292% and 315% for AUC_0–360 min and C_max over control were observed, respectively. AT1002 significantly increased the nasal absorption of molecular weight markers, PEG4000 and inulin. This study suggests that AT1002 may be used to enhance the systemic availability of macromolecules when administered concurrently.     

苓甘五味姜辛汤中4种主要成分在大鼠体内的药动学特征研究

目的：研究苓甘五味姜辛汤中4种主要成分在大鼠体内的药动学特征。方法：SD大鼠灌胃苓甘五味姜辛汤,给药后0.5,1.0,1.5,2.0,3.0,4.0,6.0,8.0,12.0,24.0 h通过眼底静脉丛采集血样。建立超高效液相色谱仪串联三重四极杆质谱（UPLC-TQ/MS）分析方法检测血清中6-姜酚、细辛脂素、芝麻脂素和6-姜烯酚的血药浓度。运用DAS 2.0药动学软件非房室模型计算C_max、T_max、t_1/2、AUC_（0-t）、AUC_（0-∞）和MRT_0-t药动学参数,绘制药时曲线。结果：建立UPLC-TQ/MS检测苓甘五味姜辛汤4种入血成分的血药浓度的方法,方法学考察结果均符合要求。运用DAS 2.0药动学软件非房室模型成功计算6-姜酚、细辛脂素、芝麻脂素和6-姜烯酚的C_max、T_max、t_1/2、AUC_（0-t）、AUC_（0-∞）和MRT_0-t等参数。结论：本研究建立了UPLC-TQ/MS检测苓甘五味姜辛汤4种入血成分的血药浓度的方法,该方法快速、灵敏、可靠,适用于该方剂的药动学研究。     

赛洛多辛及其活性代谢物在中国健康男性受试者中的生物等效性研究

目的:研究国产制剂和原研制剂赛洛多辛及其活性代谢物的生物等效性.方法:86名受试者按随机两周期交叉试验设计单剂量口服受试制剂或参比制剂4 mg,高效液相色谱-串联质谱法(LC-MS/MS)测定血浆中赛洛多辛及其活性代谢物(KMD-3213G)的浓度,WinNonlin8.0软件计算药动学参数并评价其生物等效性.结果:受...     

Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline

The steady-state serum and intrapulmonary pharmacokinetic and pharmacodynamic parameters of tigecycline were determined after intravenous administration in 30 subjects. Tigecycline was administered as a 100 mg loading dose followed by six 50 mg doses given every 12 h and was measured using HPLC/mass spectrometry. Ratios of tigecycline maximum serum concentration and area under the serum concentration–time curve to 90%—minimum inhibitory concentrations (C_max/MIC₉₀; AUC/MIC₉₀), and percentage time above MIC₉₀ were calculated for common respiratory pathogens (Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis and Haemophilus influenzae). The C_max (mean ± S.D.), AUC and half-life for serum were 0.72 ± 0.24 μg/mL, 1.73 ± 0.64 μg*h/mL and 15.0 ± 1.10 h; for lung epithelial lining fluid (ELF) the values were 0.37 μg/mL, 2.28 μg*h/mL and 39.1 h; and for alveolar cells (AC) were 15.2 μg/mL, 134 μg*h/mL and 23.7 h. Tigecycline was concentrated in AC: C_max/MIC₉₀ ratios ranged from 30.4 (H. influenzae) to 507 (S. pneumoniae); AUC/MIC₉₀ ratios ranged from 268 (H. influenzae) to 4467 (S. pneumoniae); and percentage dose interval above MIC₉₀ was 100% for the five respiratory pathogens. The C_max/MIC₉₀, AUC/MIC₉₀ ratios, T > MIC₉₀ and extended serum and intrapulmonary half-lives following the regimen used in this study are favourable for the treatment of tigecycline-susceptible pulmonary infections.     

磷酸奥司他韦干混悬剂的人体药动学与生物等效性

目的:研究磷酸奥司他韦干混悬剂在健康受试者的人体药动学和生物等效性。方法:78例受试者分别空腹和餐后口服75 mg受试制剂或参比制剂。采用高效液相色谱-串联质谱(HPLC-MS/MS)检测奥司他韦和奥司他韦酸的全血浓度,用WinNonlin 8.2软件计算药动学参数,评价两制剂生物等效性。结果:空腹试验受试制剂和参比制剂的奥司他韦C_max、AUC_0-t、AUC_0-∞分别为(52.07±23.44)和(50.54±16.09)ng·mL^-1、(150.8±32.0)和(153.6±29.3)h·ng·mL^-1、(154.2±32.2)和(157.8±30.9)h·ng·mL^-1;奥司他韦羧酸盐C_max、AUC_0-t、AUC_0-∞分别为(259.66±42.65)和(267.10±44.06)ng·mL^-1、(3 235.1±549.9)和(3 321.6±567.5)h·...