[Formulation and special investigations of innovative intraoral solid dosage forms.] / Not available.

During our work, we summarized the types of solid dosage forms which were in the focus of attention in the last years because of their innovative pharmaceutical technology solution and simple use. The biopharmaceutics of solid dosage forms for intraoral use and the advantages of the use of these dosages forms were presented in general. However, these dosage forms cannot always be prepared with conventional pharmaceutical processes, therefore the special pharmaceutical solutions which can be applied for their preparation were presented. In addition to testing the European Pharmacopoeia dosage forms, the special tests which can be applied for the characterization of innovative solid dosage forms were highlighted.

A review of omeprazole use in the treatment of acid-related disorders in children.

BACKGROUND: Acid peptic disease is a common problem, with a similar prevalence of gastroesophageal reflux disease (GERD) in adults and children. The presentation of GERD in infants and children varies from crying, irritability, or sleep disturbance to feeding difficulties, vomiting, or rumination. Helicobacter pylori (HP)-related diseases and gastric and duodenal ulcers are much more common in adults than in children, who are more likely to have gastritis or duodenitis. However, because HP infection is most likely acquired in childhood, treatment of children with endoscopically documented active HP disease may minimize the potential risk for peptic ulcer or gastric cancer in adulthood, although this is yet to be proved. OBJECTIVE: Omeprazole has been shown to be effective in the treatment of acid-related diseases. This paper reviews the literature on the use and administration of omeprazole for the treatment of GERD, peptic ulcer disease, HP infection, and other acid-related conditions in children. METHODS: Studies were identified through searches of MEDLINE and Science Citation Index for the period 1986 to November 2000, and from the reference lists of identified articles. The search terms used included omeprazole, proton pump inhibitor (PPI), children, pediatrics, routes of administration, GERD, HP infection, esophagitis, and administration. In addition, the manufacturer of omeprazole was asked for relevant unpublished information. RESULTS: Marketed and extemporaneous formulations of omeprazole have been administered to children aged 2 months to 18 years for the treatment of erosive esophagitis, gastric ulcer, duodenal ulcer, HP infection, and related conditions at dosages of 5 to 80 mg/d (0.2-3.5 mg/kg/d) for periods ranging from 14 days to 36 months with a low incidence of adverse effects. The initial dose most consistently reported to heal esophagitis and provide relief of symptoms of GERD appears to be 1 mg/kg per day. CONCLUSIONS: In uncontrolled clinical trials and case reports to date, omeprazole has been effective and well tolerated for the acute and chronic treatment of esophageal and peptic ulcer disease in children, particularly those who had failed to respond to previous treatment with histamine2-receptor antagonists. Should future long-term, controlled clinical trials in children demonstrate safety and efficacy, this PPI is likely to find a place in the armamentarium of pediatric pharmacotherapy.

Lansoprazole: a comprehensive review.

Lansoprazole is the second member of the substituted benzimidazole class of antisecretory agents approved for use in the United States. These drugs decrease parietal cell acid secretion by inhibiting H+, K(+)-adenosine triphosphatase, the final step in the secretion of acid. Lansoprazole has been studied extensively for the short-term treatment of duodenal and gastric ulcers, reflux esophagitis, and Helicobacter pylori-positive peptic ulcer disease; long-term treatment of Zollinger-Ellison syndrome; and maintenance treatment of erosive esophagitis. A dosage of 30 mg/day produced higher healing rates and equivalent or faster relief of ulcer symptoms than ranitidine or famotidine in patients with duodenal or gastric ulcers and reflux esophagitis. Compared with omeprazole 20 mg/day, that dosage provided faster epigastric pain relief in these patients after 1 week, although healing rates for the two agents were equivalent at 4 and 8 weeks. In patients with peptic ulcer refractory to 8-week therapy with histamine2-receptor antagonists, healing rates were not significantly different between lansoprazole and omeprazole. In patients with Zollinger-Ellison syndrome, lansoprazole was superior to histamine2-receptor antagonists and was similar in efficacy, safety, and duration of action to omeprazole. Combinations of lansoprazole or omeprazole with one or two antibiotics produced equivalent eradication of H. pylori. In clinical trials, lansoprazole was well tolerated, with frequency of adverse effects similar to that reported with ranitidine, famotidine, and omeprazole.

Association of vancomycin serum concentrations with outcomes in patients with gram-positive bacteremia.

We attempted to determine if an association exists between vancomycin serum concentrations resulting from traditional dosing regimens, and efficacy and toxicity outcomes. We reviewed the medical charts of 273 consecutive patients prescribed 273 courses of vancomycin therapy for documented, gram-positive bacteremia. Of the 273 courses of therapy, 45 and 31 patients met all criteria and were evaluated for toxicity and efficacy, respectively. The duration of fever and abnormal white blood cell counts, length of hospital stay, overall mortality, serum creatinine, and serum vancomycin concentrations were evaluated retrospectively. No association between initial peak or trough levels with mortality was noted. However, patients were more likely to become afebrile within 72 hours if peak and trough concentrations were 20 micrograms/ml or greater and 10 micrograms/ml or greater, respectively (p < 0.01). Patients were also more likely to have their white blood cell count return to normal within 72 hours if trough concentrations were 10 micrograms/ml or above (p < 0.01). No statistically significant correlation between nephrotoxicity and initial serum creatinine, days of hospital stay, or days of vancomycin therapy were found. Serum concentrations of vancomycin, assessed before the development of nephrotoxicity, were significantly higher in patients who became nephrotoxic. Mean (SD) trough concentrations were 23.2 (2.5) micrograms/ml and 10.2 (3.8) micrograms/ml in nephrotoxic and nonnephrotoxic patients, respectively. Our results suggest that the commonly accepted therapeutic range for vancomycin trough concentrations (< 10 micrograms/ml) may be too restrictive in patients receiving vancomycin therapy alone.

Ceftriaxone-induced acute pancreatitis.

OBJECTIVE: To report a case probable ceftriaxone-induced acute pancreatitis. CASE SUMMARY: A patient with a history of short-bowel syndrome on home total parenteral nutrition developed fever, chills, and right flank pain. She was diagnosed with gram-negative catheter sepsis and prescribed antibiotic therapy to be administered for four weeks. After completion of the first week of therapy, the antibiotic regimen was changed to intravenous injections of ceftriaxone to be given daily at home. Prior to discharge the patient developed acute abdominal pain, leukocytosis, jaundice, and markedly elevated lipase and amylase concentrations consistent with acute pancreatitis. The patient's condition improved upon discontinuation of the ceftriaxone and the remainder of her stay was uneventful. DISCUSSION: There is only one other case report in the literature of probable ceftriaxone-induced pancreatitis. Multiple other medications have been implicated in causing acute pancreatitis. The exact mechanism of this uncommon adverse effect of ceftriaxone is unknown. CONCLUSIONS: There was a temporal relationship between the development of this patient's signs and symptoms and the administration of ceftriaxone. We could not identify any other factors that may have been responsible for the development of her acute pancreatitis. Ceftriaxone should be considered as a possible etiologic agent in patients who present with acute abdominal pain and elevated lipase and amylase concentrations.

Prospective evaluation of risk factors for antibiotic-associated bleeding in critically ill patients.

A prospective surveillance program was initiated to determine the relative role of antibiotics containing N-methylthiotetrazole (NMTT) versus patient risk factors in producing antibiotic-associated bleeding. Five hundred forty-six critically ill patients with serum albumin 30 g/L or below were evaluated for evidence of a bleeding event as documented by clinical observation, hemoglobin changes, and transfusions. Bleeding events occurred in 16% of patients receiving an aminoglycoside combination, 10% receiving antibiotics with the NMTT side chain, and 14.5% receiving antibiotics not containing NMTT (p greater than 0.05). The bleeding rate was highest in febrile patients with cancer (14.5%) and lowest in those with a suspected or documented abdominal infection (10%) (p = 0.04), but within each patient group there was no difference among the antibiotics. We conclude that the use of NMTT-containing antibiotics is not an independent risk factor for bleeding, but the role of severity of illness may be underappreciated.

Superwarfarin poisoning.

Superwarfarins consist of two classes of compounds, the 4-hydroxycoumarins and the indandiones. These compounds have replaced warfarin as an anticoagulant rodenticide. This article is a summary of the clinical effects produced by accidental and deliberate ingestions of superwarfarins. Most accidental ingestions occur in childhood and result in a benign outcome. Deliberate overdoses usually involve repeated ingestions of large quantities of superwarfarins that have resulted in prolonged laboratory evidence of interference with clotting; serious bleeding has been rare. This article suggests an approach to the management of patients with accidental and deliberate anticoagulant rodenticide ingestions.

Effect of a pharmacist's and a nurse's interventions on cost of drug therapy in a medical intensive-care unit.

The effect of interventions by a pharmacist and a nurse on the cost of drug therapy in a medical intensive-care unit (ICU) was determined. A pharmacist taught cost-avoidance concepts related to medication use to a senior member of the nursing staff. The pharmacist and the nurse documented during a 91-day period all interventions that resulted in a discontinuation or change in drug therapy or involved nonformulary drug requests or serum drug concentration determinations. Costs that were avoided or added as a result of these interventions were determined using drug acquisition costs and (for interventions involving i.v. therapy) the cost of related supplies. Costs were calculated for both the initial 24-hour period after each intervention and the expected duration of therapy. The 345 interventions of the pharmacist and the nurse represented $6,383 in 24-hour cost avoidance and $23,993 in total cost avoidance. The majority of interventions resulted in discontinuation of medications or changes in drug dosage; most of those interventions involved antimicrobial agents. Other frequent interventions involved changes in route of administration and the interchange of therapeutic alternates. A pharmacist and a nurse had a positive impact on the cost of drug therapy in a medical ICU.

The effect of "superactive" charcoal and magnesium citrate solution on blood ethanol concentrations and area under the curve in humans.

Eleven healthy males between 21 and 37 years of age were enrolled into a non-randomized crossover study comparing superactive charcoal (SAC) given after ethanol administration. After receiving 0.6 gm/kg ethanol orally (95% V/V diluted in orange juice), blood was sampled at 0, 0.5, 1.0, 1.5, 2.0, 3.0, and 4.0 hours. Area under the curve (AUC) was calculated and the highest ethanol level was recorded. After a minimum of 1 week washout, the volunteers ingested an identical ethanol dose but in addition received 60 grams of SAC and 300 ml of 5.8% magnesium citrate solution 1 and 3 hours post ingestion. The data was compared using the paired t-test with p less than 0.05 considered significant. Nine volunteers completed the study. Volunteers had difficulty ingesting the full second 60 gram SAC dose. The AUC (mean 1184 mcg x hr/ml) and highest ethanol concentrations (mean 46.3 mg/dl) for the control group were not significantly greater than in the SAC group (mean AUC 1167 mcg x hr/ml and highest ethanol concentration of 49.0 mg/dl). The ethanol concentration in the SAC group was significantly less than control only at 2.0 hours (31.6 mg/dl vs 36.6 mg/dl, p less than 0.01). The peak ethanol concentration in the SAC group occurred at 1.0 hours in 7 of 9 volunteers, while in the control group, peak concentration occurred randomly between 0.5 and 2.0 hours. We conclude SAC in the dose used is not effective in decreasing AUC, highest ethanol concentration, and blood ethanol levels when given 1 and 3 hours after ethanol ingestion.

The new black magic: activated charcoal and new therapeutic uses.

Activated charcoal has been used for centuries as antidotal therapy for poisonings. New variations of charcoal therapy have developed over the last two decades. These modifications include multiple-dose activated charcoal (MDAC) therapy, charcoal hemoperfusion, and a new "superactive" charcoal (SAC). Recent literature suggests using initial charcoal therapy instead of ipecac as a first-line antidotal agent for many acute poisonings. The palatability of charcoal slurries has been enhanced by the addition of carboxymethylcellulose, sucrose, saccharin, chocolate syrup, or sorbitol. The new SAC has shown to adsorb 1.7 to 4 times the amount of substance tested compared with other activated charcoal preparations. Multiple-dose activated charcoal therapy has been shown effective in treating phenobarbital, digoxin, digitoxin, theophylline, and dapsone intoxications, among others. The problems associated with charcoal hemoperfusion therapy have been partially alleviated, and it is now alternative therapy for the seriously intoxicated patient.