| Gatifloxacin mesylate capsule is the new formulation of gatifloxacin made in. china. The study aimed to definite its pharmacokinetical charicateristic such as absorption, disposion, metablism and excretion in healthy body, and to evaluate the bioequivalence between gatifloxacin mesylate capsules and tablets to provide scientifical evidence in order to direct safe and reasonable appalication on clinic. METHODSThe study was divided into three parts. The first was to set up the analytic methodology; and the second mainly studied the pharmacokinetics of gatifloxacin mesylate capsules and tablets in body of healthy volunteers; the third studied the bioequivalence of gatifloxacin mesylate capsules and tablets in healthy volunteers . 1. Set up the analytic methodology:An HPLC method with high precision, high paricularity and sensibility was developed and validated for gatifloxacin assay in plasma samples. The mobile phase consisted of 500ml methanol,500ml water (50/50,v/v) and 3.5g dodecyl sodium sulfate (pH=3.0) .The flow rate was 1.0ml min-1 and the effect was monitored ' at 292nm. Under these conditions, the retention time of gatifloxacin was 4.84min. To evaluate the methonology by detecting the limit of quantitation for gatifloxacin in plasma, method recovery rate, draw recovery rate, RSD of inter-precision and intra-precision, selectivity and ruggedness to prove whether it could be use to study the pharmacokinetics and bioequivalence of gatifloxacin mesylate or not.2. Pharmacokinetics of Gatifloxacin mesylate capsules and Gatifloxacin mesylate tablets in healthy volunteers:Prior to trial initiation, the study protocol was approved by the Nation and the Ethic Committee of Xijing Hospital of the Fourth Military Medical University, Xi'an, Shaanxi. The 18 subjectes were informed about the study procedures and signed the informed consent form after explaining the purpose of the study. After an overnight fasting, all volunteers were given single dose of gatifloxacin mesylate capsules and gatifloxacin mesylate tablets 400 mg with 240ml of water in two times. No food was allowed until 4h after dose . administration. Water intake as allowed after 2h of dose; water, lunch and dinner were given to all volunteers according to a time schedule. They were not permitted to lie down or to sleep for the first 4h after the dose. Approximately 5ml of blood samples for Gatifloxacin mesylate assay were drawn before (Oh) and at 0.25, 0.5, 0.75, 1, 1.5, 2,3, 4, 6, 8, 12 and 24h after the dose. The blood samples were centrifuged at 10500g for 8 min at room temperature; plasma was separated and kept frozen at -20 until assayed. 100 L were injected into the HPLC system with external-standard method. The Tmax and. Cmax were actual value, and calculated the AUC (0-2-4h) andAUC(0-inf)by echelon methods; the elimination rate constant (Ke) was obtained from the least-square fitted terminal log-linear portion of the plasma concentration- time profile. The elimination half-life (T1/2) was calculated as 0.693/ Ke. MRT(o-24h) and MRT(0-inf) by pharmacokinetic statistical software of 3P97.3. Bioequivalance of Gatifloxacin mesylate tablets and Gatifloxacin mesylate capsules in healthy volunteers:This study was based on a single dose, randomized, two-treatment, two-period crossover design. 18 volunteers were divided into two groups that A and B, In the morning of phase I , after an overnight fasting volunteers were given single dose of gatifloxacin mesylate capsules and gatifloxacin mesylate tablets 400 mg with 240ml of water respectively. Attention in the experience was the same as the second part. Approximately 5ml of blood samples for gatifloxacin mesylate assay were drawn before (Oh) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24h after the dose. The blood samples were centrifuged at 10500 x g for 8 min at room temperature; plasma was separated and kept frozen at -20 until assayed. After a washout period of 7d the study was repeated in the same manner to complete the crossover design. The g...
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