AIMThe simplified preparative method and formulation for atenolol monolithic osmotic pump tablets were investigated.

METHODSThe core tablets with an indentation were compressed by the punch with a needle. Osmotic pump tablets were prepared by coating the indented tablets. Similarity factor was used to evaluate formulation of osmotic pump tablets.

RESULTSThe formulation of core tablets and the composition and thickness of coating membrane showed marked effects on drug release. Orifice size of core tablets in the range of 1.00 - 1.14 mm scarcely affected drug release.

CONCLUSIONThe preparation of osmotic pump tablets was simplified with the exempting of laser drilling. The atenolol monolithic osmotic pump tablets could deliver drug constantly for 24 h.

Adrenergic beta-Antagonists ; administration & dosage ; chemistry ; Atenolol ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Osmosis ; Polyethylene Glycols ; chemistry ; Tablets ; Technology, Pharmaceutical ; methods

PURPOSE: The aim of this study was to evaluate the effects of premedication with oral atenolol or enalapril, in combination with remifentanil under sevoflurane anesthesia, on intraoperative blood loss by achieving adequate deliberate hypotension (DH) during orthognathic surgery. Furthermore, we investigated the impact thereof on the amount of nitroglycerin (NTG) administered as an adjuvant agent. MATERIALS AND METHODS: Seventy-three patients undergoing orthognathic surgery were randomly allocated into one of three groups: an angiotensin converting enzyme inhibitor group (Group A, n=24) with enalapril 10 mg, a beta blocker group (Group B, n=24) with atenolol 25 mg, or a control group (Group C, n=25) with placebo. All patients were premedicated orally 1 h before the induction of anesthesia. NTG was the only adjuvant agent used to achieve DH when mean arterial blood pressure (MAP) was not controlled, despite the administration of the maximum remifentanil dose (0.3 microg kg-1min-1) with sevoflurane. RESULTS: Seventy-two patients completed the study. Blood loss was significantly reduced in Group A, compared to Group C (adjusted p=0.045). Over the target range of MAP percentage during DH was significantly higher in Group C than in Groups A and B (adjusted p-values=0.007 and 0.006, respectively). The total amount of NTG administered was significantly less in Group A than Group C (adjusted p=0.015). CONCLUSION: Premedication with enalapril (10 mg) combined with remifentanil under sevoflurane anesthesia attenuated blood loss and achieved satisfactory DH during orthognathic surgery. Furthermore, the amount of NTG was reduced during the surgery.
Administration, Oral ; Adrenergic beta-Antagonists/administration & dosage/*pharmacology ; Adult ; Aged ; *Anesthesia, Inhalation ; Atenolol/administration & dosage/*pharmacology ; Blood Loss, Surgical ; Blood Pressure/drug effects ; Cardiac Output/drug effects ; Double-Blind Method ; Enalapril/administration & dosage/*pharmacology ; Female ; Heart Rate/drug effects ; Humans ; Intraoperative Care ; Male ; Methyl Ethers/*administration & dosage ; Middle Aged ; *Orthognathic Surgical Procedures ; Piperidines/*administration & dosage ; *Premedication ; Treatment Outcome

BACKGROUND: Carvedilol is a direct inhibitor of vascular smooth muscle cell migration and proliferation through inhibition of mitogen-activated protein kinase activity and regulation of cell cycle progression. It produced an 84% suppression of neointimal hyperplasia in rat carotid angioplasty model, but no data are available regarding its effect on stent restenosis in patients. We tested whether a sustained oral administration of carvedilol reduces restenosis after coronary stenting in patients. METHODS: One hundred fifty nine patients were randomized to receive either carvedilol (50 mg/day, n=80) or atenolol (50 mg/day, n=79) at least 1 day before stenting and continued on the same medication over 3 months. The primary end point was angiographic restenosis (>50% diameter stenosis) at follow-up angiography. RESULTS: Baseline clinical and angiographic variables were similar between the carvedilol and atenolol group. The carvedilol dose was tolerable in most patients after adjustment of other medications, but reduced in 3 patients due to hypotension and dizziness. Angiographic follow-up was done in 137 patients (86%) and the restenosis rate was not different significantly between both groups (17.1% versus 19.4%, p=0.732). CONCLUSION: A sustained oral administration of carvedilol is not effective to reduce stent restenosis. With carvedilol targeting regulators of cell cycle progression and having a profound neointimal inhibition with a high blood concentration in an experiment, further investigations using a stent-based delivery to achieve a high local concentration may be warranted.
Administration, Oral ; Angiography ; Angioplasty ; Animals ; Atenolol ; Cell Cycle ; Cell Movement ; Coronary Restenosis ; Dizziness ; Drug Therapy ; Follow-Up Studies ; Humans ; Hyperplasia ; Hypotension ; Muscle, Smooth, Vascular ; Prospective Studies* ; Protein Kinases ; Rats ; Stents*