In this comparative bioavailability study two tablet formulations of atenolol (sales and clinical trial) were compared with an oral solution. Twelve healthy adult male volunteers received, on a cross-over basis, on three separate occasions, 100 mg oral dose of the three formulations of atenolol. Bioavailability was based on concentrations of atenolol in whole blood and urine. The atenolol blood levels peaked at approximately 3 h after dosing, with individual values ranging from 0.21 to 0.92 microgram ml-1 (a four-fold difference), with all three formulations. Three-fold variations among subjects occurred in the areas under the curve (AUC) and urinary recoveries. The average elimination of half-life of atenolol was between 6 and 7 h for all three formulations. Some statistically significant differences were observed between the tablets and the aqueous solution: the AUC (infinity) and mean peak blood concentrations were significantly greater with the U.K. sales tablet than the solution, and the mean concentrations in the blood at certain specified times after administration were significantly greater with the two tablet formulations than the solution. The profiles of absorption and excretion of the two tablet formulations were similar. No adverse reactions were encountered in this study and all subjects completed the study without incidence.

Adult↗

PubMedDate not supplied

Bioavailability of sustained release propranolol formulations.

In this comparative bioavailability study two sustained release capsule formulations of propranolol, one a clinical trial formulation and the other the U.K. sales formulation ('Inderal' LA), were compared with a conventional 'Inderal' tablet. Twelve healthy adult male volunteers received, on cross-over basis, on three separate occasions, 160 mg oral doses of three formulations of 'Inderal'. Bioavailability was based on concentration of propranolol in whole blood. The peak blood level and area under the propranolol blood level curve fell as the dissolution time increased. The half-lives of the three formulations were inversely proportional to their dissolution rates, those of the sustained release formulations being considerably longer than that of the conventional tablet. The 160 mg 'Inderal' tablet produced a rapid 90-fold decline over 24 h in propranolol blood levels following a high initial peak. By comparison both sustained release formulations showed a less rapid fall in systemic levels and gave higher blood levels at the end of 24 h and plateau values between 8 and 14 ng ml-1. The 'Inderal' LA sustained release formulation gave consistently higher propranolol blood levels than the clinical trial sustained release formulation. This result is in good agreement with their dissolution profiles. The lowering of the systemic bioavailability as the dissolution time increases is thought to be due to an increased metabolism of propranolol.

Adult↗

PubMedDate not supplied

Bioavailability in man of atenolol and chlorthalidone from a combination formulation.

In this comparative bioavailability study in 12 healthy volunteers the blood level profiles and urinary recoveries of both atenolol and chlorthalidone were studied following the administration of the drug as a fixed combination ('Tenoretic'), as a free combination, and individually, at doses of 100 mg atenolol, and 25 mg chlorthalidone. There were no statistically significant differences between the three formulations of atenolol in terms of individual blood levels, half-life, area-under-the-curve, and urinary excretion. The half-lives were between 5 and 6 h in agreement with other published data. Thus the bioavailability of atenolol from the fixed combination is equivalent to that from the free combination and from the atenolol tablet. The chlorthalidone blood levels were slightly higher following the administration of the fixed combination when compared with the free combination or the chlorthalidone tablet. This observation was reflected in estimates of the area under the curves and the urinary recoveries. The half-lives of all three formulations were similar at about 60 h. It is concluded that combining chlorthalidone and atenolol in a single tablet does not reduce the systemic bioavailability of either component.

Adult↗

PubMedDate not supplied

Bioavailability of propranolol and bendrofluazide formulations.

In this comparative bioavailability study in 12 healthy volunteers the blood level profiles of both propranolol and bendrofluazide were studied following the multiple oral administration of the drugs as a fixed combination (Inderetic) and as a free combination at doses of 80 mg propranolol twice daily and 2.5 mg bendrofluazide twice daily. There were no statistically significant differences between the two regimens in terms of individual propranolol blood levels, half-lives and areas under the curve. The half-lives were between 5 and 8 h. Thus the bioavailability of propranolol from the fixed combination is equivalent to that from the free combination. The mean peak bendrofluazide blood levels were slightly higher following the administration of the fixed combination. This difference was statistically significant only at 1 and 2 h after the first dose. There were no statistically significant differences between these two bendrofluazide regimens in terms of half-life and area under the curve. Thus the bioavailability of bendrofluazide from the fixed combination is equivalent to that from the free combination. It is concluded therefore that by combining bendrofluazide and propranolol in a fixed capsule formulation does not affect significantly the systemic bioavailability of either component.

Adolescent↗

PubMedDate not supplied

Bioavailability in man of atenolol and chlorthalidone from a combination formulation.

In this comparative bioavailability study in 12 healthy volunteers the blood level profiles and urinary recoveries of both atenolol and chlorthalidone were studied following the administration of the drugs as a fixed combination ('Tenoret 50'), as a free combination, and individually, at doses of 50 mg atenolol and 12.5 mg chlorthalidone. There were no statistically or clinically significant differences between the three treatments of atenolol in terms of individual blood levels, areas under the curve, and urinary excretion. The mean half-lives were between 5 and 7 h, in agreement with other published data. The variation in peak systemic levels is less than that observed for a number of other beta-blocking drugs and is of the same order as seen in other investigations involving atenolol. Thus the bioavailability of atenolol from the fixed combination is equivalent to that from the free combination and from the atenolol tablet. The mean peak blood concentrations of chlorthalidone were 0.94, 1.00, and 0.99 micrograms ml-1 for the fixed and free combinations and the chlorthalidone tablet, respectively. The mean areas under the curve were also similar as were the mean half-lives and urinary recovery. There were no statistically or clinically significant differences between the three treatments. Thus the bioavailability of chlorthalidone from the fixed combination is equivalent to that from the free combination and from the chlorthalidone tablet. It is concluded that combining chlorthalidone and atenolol in a single tablet does not affect the systemic bioavailability of either component.

Adult↗

PubMedDate not supplied

Polyethylene glycol conjugated interleukin-2: clinical and immunologic effects in patients with advanced renal cell carcinoma.

Recombinant interleukin-2 (rIL-2) modified with monomethoxypolyethylene glycol (PEG IL-2) was utilized in patients with metastatic renal cell carcinoma in two separate multi-institutional trials. PEG IL-2 was administered as an I.V. bolus days 1, 8, 15, and 22 with cycles repeated every six weeks. The two trials employed different dose levels: A) 20 x 10(6) I.U./m2 day 1 followed by 12 x 10(6) I.U./m2 days 8, 15, 22; and B) 12 x 10(6) I.U./m2 days 1, 8, 15, 22. Thirty-five patients were entered and 31 were evaluable for response (A-15/18, B-16/17). Two of 31 patients had partial responses. Median therapy duration was four weeks (range 1-15), and dose reduction for grade III or IV toxicity was required in 14/35 patients (A-6/18, B-8/17). Toxicity (> or = grade III) seen included: hypotension 51%, dyspnea 17%, seizures 6%, and mental status changes 11%. No differences in response or toxicity between the two schedules were noted. Hematologic changes included lymphocytosis and eosinophilia in the majority of patients. PEG IL-2 given once weekly has significant toxicity, and may produce tumor regression in patients with renal cell carcinoma.

Adult↗

PubMedDate not supplied

Simple but sophisticated immobilization casts.

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Head and Neck Neoplasms↗

PubMedDate not supplied

Relationship of psychiatric morbidity and psychosocial factors in organ transplant candidates.

The purpose of this study was to explicate the statistical relationship between psychiatric diagnosis and psychosocial adjustment and health status in organ transplant candidates. Interview and psychometric data were obtained from 311 heart, kidney, lung, and liver transplant candidates. Over 60% of the cases met criteria for DSM-III-R Axis I diagnoses, nearly 32% for Axis II disorders. Axis II disorders were significantly associated with medical compliance problems, whereas Axis I disorders were predominantly associated with poorer psychosocial adjustment and health status. Nearly one-quarter of the patients had comorbid Axis I and Axis II disorders, and evidenced poorest premorbid coping and degree of marital harmony, defining a subgroup at special risk for problematic outcome. The incidence of psychiatric disorders and their association with lack of psychosocial resources and poor physical health supports the use of systematic, multidisciplinary assessment of transplant candidates.

Adaptation, Psychological↗

PubMedDate not supplied

When the case manager becomes the patient.

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Adult↗

PubMedDate not supplied

Recovery following laparoscopic cholecystectomy in either a 23 hour or an 8 hour facility.

Research confirms that laparoscopic cholecystectomy (LC) results in shorter lengths of hospital stay and earlier return to usual activity than the traditional cholecystectomy procedure. Research in this area, however, focuses more on the medical aspects of patient recovery, but very few studies have evaluated how these patients manage their recovery at home or what types of problems they encounter. A total of 28 LC patients were randomly assigned to two groups: (1) 23 h stay (overnight) in a general surgical ward or (2) day procedure unit (DPU) stay. Data was collected by a self-administered Postoperative Symptoms Diary and telephone interview. Results showed no significant difference between the two groups of patients recovery symptoms scores. Problems with mobility, pain and elimination recorded the highest mean scores for both groups of patients. Overnight patients also experienced problems with tiredness and eating. All DPU patients were able to manage their postoperative symptoms, compared to only 44% of patients who had stayed in overnight. Carer assistance was needed with regard to activities of daily living, child care and reassurance. Results showed that with careful selection of patients, LC cases performed as day procedures did not impact at all on the patients' recovery trajectory.

Adolescent↗

PubMedDate not supplied

Endoscopic skull base surgery II: a new animal model for surgery of the posterior fossa.

The field of skull base surgery has been influenced by a general philosophy that currently exists in modern surgical practice favoring less invasive means of managing surgical disease. Adapting techniques developed by general surgeons and other surgical subspecialists, skull base surgeons are now experimenting with endoscopy to resect tumors, manage vascular lesions, and manipulate critical intracranial structures. Lesions formerly requiring significant soft tissue dissection and craniotomy for exposure are now potentially amenable to treatment via a keyhole approach. As in other surgical specialties, however, a reliable animal model is necessary for experimentation with and development of new endoscopic techniques in the skull base. The swine provides just such a model, primarily due to craniofacial and skull base relationships that are analogous to humans. We have focused on the posterior skull base of the swine in this experiment: Via a retrosigmoid craniotomy we opened the dura of the posterior fossa and used endoscopes to visualize and manipulate the critical structures in this area. The cerebellum and midbrain were appreciated, as were cranial nerves V, VII, VIII, IX, X, and XI. Blood vessels on the surface of the midbrain were also identified. This experience further supports the use of the swine as an appropriate animal model for endoscopic skull base surgery.

Animals↗