Rate-controlled rectal drug delivery in man with a hydrogel preparation

Cylindrical hydrogels of hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent were prepared by radical polymerization at 70°C. After washing they were soaked in an aqueous drug solution of antipyrine or theophylline. The in vitro drug release experiments were performed in 100 ml isotonic glucose at 37°C. Rectal administration of a hydrogel preparation containing antipyrine was performed in two subjects for 72 h. With a theophylline-containing hydrogel preparation rectal drug administration was performed in six volunteers for 24 h. Plasma and saliva samples were taken regularly and the in vivo drug release was determined by means of a deconuolution procedure. In vitro 1.12g antipyrine had been released according to a matrix-type profile for 72 h, whereas it was calculated that this was 1.13 and 1.09 g in vivo in the two subjects. The release profile in vivo was very similar to that in vitro. The theophylline hydrogel preparation released in vitro a total of 288 ± 6 mg of drug in 24 h and in vivo this amount was calculated to be 288 ± 11 mg (mean ± s.d.). Near-constant plasma theophylline concentrations were obtained after administering the hydrogel preparation. In all six subjects the cumulative drug profile was in almost perfect agreement with that observed in vitro. Hydrogels offer interesting perspectives as rate-controlled rectal drug delivery systems because of the predictable release profile in vivo on the basis of observations in a simple in vitro model

Theory for incongruent crystallization: application to a ZBLAN glass

Equations which describe incongruent nucleation and subsequent crystal growth are derived. A ZrF4-BaF2-LaF3-AlF3-NaF (ZBLAN) glass was used to test the validity of these equations. Nucleation rate measurements were fitted to theory and some growth rate measurements were in reasonable agreement with theor. predictions. Both nucleation theory and crystal growth theory were used for computer simulations of the crystn. behavior during heat treatments. Some heat treatments were performed in a DSC app. to verify the theories. The exptl. results were in good agreement with the numerical data. Using these theor. results it is possible to est. fiber scattering losses due to crystn. Depending on drawing temp., estd. losses can vary from 0.014 (310 Deg) to >=25 decibel/km (320 Deg). [on SciFinder (R)

E1A functions as a coactivator of retinoic acid-dependent retinoic acid receptor-beta 2 promoter activation

The retinoic acid (RA) receptor (RAR) beta 2 promoter is strongly activated by RA in embryonal carcinoma (EC) cells. We examined this activation in the P19 EC-derived END-2 cell line and in E1A-expressing counterparts and found strong RA-dependent RAR beta 2 promoter activation in the E1A-expressing cells, which was not observed in the parental cell line, indicating a possible role for E1A in RAR beta 2 activation. In transient transfection assays, E1A functioned as a coactivator of RA-dependent RAR beta 2 promoter activation and, moreover, was able to restore this activation in cells lacking RAR beta 2 activation. By deletion analysis, two regions in the RAR beta 2 promoter were identified that mediate the stimulatory effect of E1A: the RA response element and TATA box-containing region and a more up-stream region between -180 and -63, in which a cAMP response element-related motif was identified as a target element for E1A. In addition, determination of endogenous E1A-like activity by measuring E2A promoter activity in transient transfection assays in EC and differentiated cells revealed a correlation between RA-dependent RAR beta 2 promoter activation and the presence of this activity, suggesting an important role for the cellular equivalent of E1A in regulation of the RAR beta 2 promoter

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaig

First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial

The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin-gemcitabine (CG) or epirubicin-gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n = 240) were randomised to receive gemcitabine 1125 mg m(-2) (days 1 and 8) plus either cisplatin 80 mg m(-2) (day 2) or epirubicin 100 mg m(-2) (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status less than or equal to2. QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 questionnaires. There were no significant differences in median progression-free survival (CG 26 weeks, EG 23 weeks), median overall survival (CG 43 weeks, EG 36 weeks), or tumour response rates (CG 46%, EG 36%). Toxicity was mainly haematologic. In the EG arm granulocytopenia occurred more frequently, leading to more febrile neutropenia. Also, elevation of serum transaminases, mucositis, fever, and decline in LVEF were more common in the EG arm. In the CG arm, more patients experienced elevated serum creatinine levels, sensory neuropathy, nausea, and vomiting. Global QOL was not different in both arms. Progression-free survival, overall survival, response rate, and QOL were not different between both arms; however, overall toxicity was more severe in the EG arm

Prospective Clinical and Pharmacological Evaluation of the Delcath System's Second-Generation (GEN2) Hemofiltration System in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan

Surgical oncolog

Prospective clinical and pharmacological evaluation of the Delcath System’s second generation (GEN2) hemofiltration system in patients undergoing percutaneous hepatic perfusion with melphalan

Surgical oncolog