[A multi-center, randomized, controlled, double blind and double dummy clinical trial of antofloxacin hydrochloride tablet versus levofloxacin tablet for the treatment of acute bacterial infections].

OBJECTIVE: To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. METHODS: A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was closed as controlled drug. The duration of treatment was 7-14 days in both groups. RESULTS: A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for per-protocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS) population were 79.7% and 77.4%, the effective rates were 95.2% and 96.7%, and the bacterial clearance were 96.7% and 97.5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety. The drug adverse events occurred both in 10.1%, and drug adverse reactions occurred in 7.8% and 7.9% patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prolongation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P > 0.05). CONCLUSIONS: Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

Pharmacokinetics and bioequivalence study of valacyclovir hydrochloride capsules after single dose administration in healthy Chinese male volunteers.

The aim of the present study was to compare the bioavailability of valacyclovir (CAS 124832-26-4; INN: valaciclovir) from two valacyclovir hydrochloride (CAS 214832-27-5) capsules (150 mg/capsule as test preparation and 150 mg/capsule commercially available original capsule of the drug as reference preparation) in 20 Chinese healthy male volunteers, aged between 20 and 27. The study was conducted according to an open, randomized, single blind, 2-way crossover study design with a wash-out phase of 7 days. Blood samples for pharmacokinetic profiling were taken up to 24 h post-dose. Valacyclovir hydrochloride is rapidly converted to acyclovir (CAS 59277-89-3) after oral administration, so the pharmacokinetics and bioequivalence of valacyclovir hydrochloride can be studied by determining the plasma concentration of acyclovir. Plasma concentrations of acyclovir were determined with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters of test and reference formulations were estimated as follows: the maximum plasma concentrations (C(max)) were 2.04 +/- 0.43 microg/mL and 2.01 +/- 0.50 microg/mL; the median T(max) were 1.1 +/- 0.3 h and 1.0 +/- 0.3 h; plasma elimination half-lives (t1/2) were 2.94 +/- 0.42 h and 2.85 +/- 0.28 h. Values of AUC(0-t) demonstrate nearly identical bioavailability of valacyclovir hydrochloride from the examined formulations. AUC(0-15) were 6.70 +/- 1.26 microg x h/ mL and 6.96 +/- 1.25 microg x h/mL. Areas under the plasma concentration-time curve (AUC(0-infinity)) were 6.90 +/- 1.30 microg x h/mL and 7.15 +/- 1.31 microg x h/mL. Both primary target parameters, AUC(0-infinity) and AUC(0-t) were tested parametrically by analysis of variance (ANOVA) and relative bioavailabilities were 96.69 +/- 7.89% for AUC(0-infinity), 96.40 +/- 8.0% for AUC(0-15). Bioequivalence between test and reference preparation was demonstrated for both parameters, AUC(0-infinity) and AUC(0-t). The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80-125%. It meant that the test formulation was bioequivalent to the reference formulation for valacyclovir hydrochloride.

A sensitive and practical LC-MS/MS method for the determination of mizoribine in human serum and its bioequivalence study on Chinese healthy volunteers.

A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of mizoribine in human serum using thiamphenicol as internal standard (IS). The serum samples of mizoribine were precipitated with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase of 0.1% ammonium acetate water solution-methanol (47:53, v/v). Mizoribine and IS were detected in the multiple reaction monitoring mode with precursor/product ion transitions of m/z 258.2/126.0 and 354.1/185.2, respectively. The calibration curves were linear over the range of 0.02-2 microg mL(-1) for mizoribine. The limit of quantification (LOQ) was 0.02 microg mL(-1) with acceptable precision and accuracy. The validated method was successfully applied for the evaluation of a bioequivalence study on Chinese healthy volunteers. The main pharmacokinetics parameters after oral administration of 100 mg mizoribine test or reference formulation were as follows: Cmax (1.00 +/- 0.21), (1.00 +/- 0.22) microg mL(-1); AUC(0-infinity) (6.72 +/- 1.39), (6.48 +/- 1.44) microg h mL(-1); t1/2 (2.77 +/- 0.26), (2.66 +/- 0.29) h; tmax (2.95 +/- 0.78), (2.84 +/- 0.50) h.

Bioequivalence of two tablet formulations of helicidum adminstered in single dose to healthy Chinese volunteers.

In this 2 x 2, randomized, crossover bioequivalence study, two tablet preparations of helicidum were compared in 20 healthy Chinese male subjects. The drug was given in a single dose of three tablets (75 mg) and blood samples were withdrawn during 12 h after drug administration. Helicidum was separated and analyzed using a validated liquid chromatography-mass spectrum method. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The primary calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two preparations, using various statistical methods. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range (80-120%) for bioequivalence. Based on these statistical inferences it can be concluded that the two tablet preparations of helicidum are likely to be bioequivalent.

[Phase II randomized clinical trail of zoledronic acid in treating metastatic bone pain of malignancy].

BACKGROUND & OBJECTIVE: Bone metastases are the prevailing reason for pain in patients with malignancies, which seriously affect their life quality. Zoledronic acid, the third generation of bisphosphonates, can inhibit the activity of osteoclasts and relieve pain. This study was to evaluate the efficacy and safety of zoledronic acid in treating metastatic bone pain for patients with malignancies. METHODS: A multi-center, randomized, double-blind, and prospective trail was conducted. Patients with metastatic bone pain were randomized to receive zoledromic acid plus monnitol, or pamidronate plus monnitol as positive control. RESULTS: From Oct. 2003 to Oct. 2004, 216 patients with metastatic bone pain were randomized into 2 groups: 109 in zoledromic acid group, and 107 in pamidronate group. There was no significant difference in pain intensity (PI) between zoledromic acid group and pamidronate group before treatment (6.0+/-1.1 vs. 6.0+/-1.3, P=0.938), 7 days after treatment (3.7+/-1.99 vs. 4.1+/-2.0, P=0.119), and 14 days after treatment (3.2+/-2.0 vs. 3.7+/-2.4, P=0.129). The differences in complete response (CR) rate, partial response (PR) rate, and total response rate between the 2 groups were not significant (10.4% vs. 9.5%, 69.8% vs. 69.5%, 88.7% vs. 85.7%, P>0.05). Time to CR was significantly shorter in zoledromic acid group than in pamidronate group [(7.0+/-2.2) days vs. (9.5+/-2.6) days, P=0.033]; the differences in time to PR, duration of CR, and duration of PR between the 2 groups were not significant [(4.9+/-2.6) days vs. (5.0+/-2.5) days, P=0.908; (13.2+/-1.80) days vs. (14.0+/-0.0) days, P=0.155; and (13.4+/-1.9) days vs. (12.8+/-2.8) days, P=0.127]. The main adverse events were fever, nausea, vomiting, and general malaise. The occurrence and severity of adverse events were similar between the 2 groups. CONCLUSION: Zoledromic acid is effective and safe in treating metastatic bone pain of patients with malignancy, which is similar to pamidranate.

Determination of loratadine in human plasma by HPLC with fluorescence detector and study on its bioavailability.

AIM: To establish an HPLC-fluorescence method for determination of loratadine in human plasma and evaluate its relative bioavailability. METHODS: An Alltech-C18 column and a mobile phase of acetonitrile-water-glacial acetic acid-triethylamine (90:100:6:0.15) were used. The fluorescence detector was set at Ex 274 nm, Em 450 nm. The flow rate was 1 mL.min-1. RESULTS: The calibration curve was linear over a concentration range of 0.2-30 micrograms.L-1. The limit of quantification was 0.2 microgram.L-1. The average method recoveries varied from 96% to 98%. The results showed AUC, Tmax, Cmax and T1/2 beta between the testing tablets, testing capsules and reference tablets had no significant difference (P > 0.05). Relative bioavailabilities were 107% +/- 17% and 100% +/- 14% respectively. CONCLUSION: The three formulations were bioequivalent.