Pharmacokinetics of amoxicillin in obese and nonobese subjects.

AIMS: To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. METHODS: A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. RESULTS: Ten nonobese subjects (mean age 30.6 ± 7.12 y; body mass index 21.56 ± 1.95 kg/m2 ) and 20 obese subjects (mean age 34.47 ± 7.03 y; body mass index 33.17 ± 2.38 kg/m2 ) participated in the study. Both maximum concentration (Cmax ; 12.12 ± 4.06 vs. 9.66 ± 2.93 mg/L) and area under the curve (AUC)0-inf (34.18 ± 12.94 mg.h/L vs. 26.88 ± 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 ± 17.85 L vs. 27.57 ± 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, Cmax , V/F and clearance, and for creatinine clearance vs. AUC, Cmax and clearance. CONCLUSION: In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.

Design and Characterization of Mucoadhesive Gelatin-Ethylcellulose Microparticles for the Delivery of Curcumin to the Bladder.

BACKGROUND: Bladder cancer is the second type of malignant carcinoma of the urinary tract. The treatment is time-consuming and requires maintenance doses of the drug for long period of time with important side effects. Curcumin has shown evident clinical advances in the treatment of cancer. The technology of microencapsulation and the use of mucoadhesive materials can contribute to modify the delivery and improve the bioavailability of curcumin. OBJECTIVE: The aim of this study was to design and characterize mucoadhesive microparticles containing curcumin using multivariate analysis and the spray-drying technique. METHODS: A factorial design 32+1 was employed to investigate the influence of gelatin, ethylcellulose, and curcumin on size, polydispersity index, drug content and entrapment efficiency. Microparticles were also evaluated by ATR-FTIR, X-ray diffraction, antioxidant activity, in-vitro release profile, exvivo mucoadhesion performance, and in-vitro cytotoxicity. RESULTS: Microparticles showed non-uniform surface, mean diameter from 2.73 µm to 4.62 µm and polydispersity index from 0.72 to 1.09, according to the different combinations of the independent factors. These independent variables also had a significant effect on the drug content. The highest values of drug trapping efficiency were obtained with the highest concentration of curcumin and polymers. Formulations displayed slow drug release and important antioxidant activity. The good mucoadhesive performance of microparticles was assessed by the falling film technique. Moreover, the formulations did not display in vitro toxicity against Artemia salina and Fibroblasts LM(TK). CONCLUSION: The design results were useful for developing of curcumin dosage form with good physicochemical characteristics and mucoadhesive properties for the bladder administration.