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Biomedical subjects

R J Anders

Publications and source records attributed to R J Anders.

7 recordsLinked to original sources

Nocturnal dosing of a novel delivery system of verapamil for systemic hypertension. Verapamil Study Group.

To evaluate the efficacy and safety of a novel delivery system of physiologic pattern release (PPR)-verapamil administered nocturnally to patients with stages I and II hypertension using ambulatory blood pressure (BP) monitoring, we performed a multicenter (17 centers), double-blind, randomized, placebo-controlled, parallel-group trial with placebo and 120, 180, 360, and 540 mg of verapamil in 287 randomized patients. The delivery system has a delay in the release of verapamil for 4 to 6 hours, and then delivers the drug from an osmotic pumping system for approximately 12 hours. Patients were dosed at 10 P.M. The primary end point was change from baseline in trough diastolic BP assessed by ambulatory BP monitoring from 6 to 10 P.M. after 8 weeks of therapy, whereas secondary measures included changes from baseline in peak, early morning (6 to 10 A.M.) systolic and diastolic BP, trough clinic BP, and 24-hour average daytime (8 A.M. to 8 P.M.) and nighttime (8 P.M. to 8 A.M.) BP. The 180, 360, and 540 mg verapamil doses achieved statistically significant reductions in trough (6 to 10 P.M.) diastolic BP (-3.9 +/- 1.0, -7.8 +/- 1.2, and -10.6 +/- 1.1 mm Hg, respectively). Reductions in peak early morning (6 to 10 A.M.) diastolic BP were greater (-4.6 +/- 0.9, -13.3 +/- 1.2, and -19.0 +/- 1.2, for 180, 360, and 540 mg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

Placebo-controlled evaluation of three doses of a controlled-onset, extended-release formulation of verapamil in the treatment of stable angina pectoris.

This double-blind, placebo-controlled, parallel-group, multicenter study was designed to evaluate the safety and efficacy of a new controlled-onset, extended-release formulation of verapamil hydrochloride called physiologic pattern release (PPR) verapamil. The study was conducted at 24 sites (13 United States, 5 Canada, 6 overseas; see Appendix). Following a 1- to 3-week single-blind placebo lead-in period, 278 patients with chronic stable angina pectoris (247 males, 31 females, mean age 60.8 years, range 32 to 78) were randomly assigned to 1 of 4 once-daily, fixed-dose treatment groups: verapamil 180, 360, or 540 mg, or placebo. PPR verapamil at all doses significantly increased (p < 0.05) time to moderate angina and symptom-limited exercise duration, and verapamil 360 mg significantly increased (p < 0.05) time to > or = 1 mm ST-segment depression, after 4 weeks of treatment when assessed 24 hour after the previous dose. Larger doses of verapamil were associated with proportionately greater improvements in exercise tolerance. Frequency of anginal attacks was also reduced by verapamil. The most frequently observed adverse events were dizziness, headache, constipation, and nausea. The incidence of constipation was high (20.9%) within the 540 mg treatment group. This verapamil formulation can be clinically titrated within a 180 to 540 mg dosing range, permitting effective once-daily administration for the treatment of chronic stable angina.

Adult

Comparison of EMIT versus bioassay to evaluate inactivation of tobramycin by piperacillin.

We evaluated and compared the sensitivity of enzyme multiplied immunoassay (EMIT) and bioassay techniques in detecting the degree of inactivation of tobramycin by piperacillin in serum specimens. Specimens were prepared to contain initial tobramycin concentrations of 10 micrograms/ml and piperacillin concentrations of 62.5, 125.0, 250.0, and 500 micrograms/ml. The samples were stored at room temperature (25 degrees C), in the refrigerator (4 degrees C), and in the freezer (-10 degrees C) for up to 7 days. Tobramycin concentrations were determined by the two assay methods at the conclusion of 1, 3, and 6 h and 1, 3, 5, and 7 days of storage. The percentage of tobramycin activity as measured by EMIT and bioassay differed throughout the study period. Statistical analysis revealed that the assay method was the only significant variable to contribute to the variability observed in the differences of tobramycin concentration. Our results suggest that the bioassay technique is more sensitive than the EMIT assay for detecting the degree of inactivation of tobramycin by piperacillin. The EMIT assay overestimates tobramycin concentrations, which may be due to measurement of active and inactive tobramycin.

Analysis of Variance

Lower incidence of doxorubicin-induced cardiomyopathy by once-a-week low-dose administration.

A review of the literature investigating an alternative method of administering doxorubicin on a weekly basis demonstrates a lower incidence of doxorubicin-induced cardiomyopathy, as judged by endomyocardial biopsy techniques and by an apparent lower incidence of CHF as compared to older reports in the literature utilizing conventional tri-weekly administration. However, none of these studies has utilized objective methods for verifying cardiac function. The precise reason why weekly administration may induce lesser degrees of damage to the myocardium is not clearly understood. However, it appears that the lower serum concentrations obtained with this dosing regimen result in lower myocardial tissue concentrations of the drug. Though the initial data are encouraging, larger clinical trials are necessary to establish a lower incidence of cardiotoxicity with weekly low-dose doxorubicin administration. Such studies, if specifically designed to evaluate changes in myocardial function, will resolve the questions and hopefully establish the advantages of this encouraging new therapeutic modality.

Animals

Compatibility of intravenous drugs in a coronary intensive care unit.

In a coronary intensive care unit (CCU) it is often necessary to utilize extensive pharmacologic interventions and multiple intravenous medications in order to stabilize a critically ill patient. However, the necessity of several intravenous infusions often presents the problem of compatibility of these medications when infused within a common line. The pharmacist must possess adequate skill to identify potential incompatibilities by retrieving information on the physical and chemical compatibilities of various intravenous medications. In a critical care setting, time is an important factor, and information that can be obtained rapidly and reliably is vital for the pharmacist to prevent the administration of an irritating substance or a medication that has undergone deterioration as a result of chemical inactivation. A compatibility table containing the most commonly used drugs in a CCU has been developed based on currently available literature, including standard reference texts, about these medications. The table outlines the potential for interactions, within a single intravenous line, when several drugs are infused concurrently. In addition, a review of the concepts of physical and chemical incompatibility is presented. The stability of an admixture is defined utilizing requirements established in the USP NF monographs and manufacturers' specifications. The resulting table concisely organizes vital information in a form that allows rapid, accessible information to the pharmacist in a critical care setting, where it is most needed.

Chemistry, Pharmaceutical

Overflow urinary incontinence due to carbamazepine.

We describe the first well documented case of overflow urinary incontinence owing to prolonged carbamazepine treatment for temporal lobe seizures. Carbamazepine increased the bladder capacity to 1,700 ml. and was accompanied by symptoms of urgency and frequency. After carbamazepine was discontinued and the patient was given primidone the voiding symptoms disappeared. Post-voiding catheterization of the bladder showed minimal residual urine volume. In a review of urological adverse reactions of anticonvulsant drugs that are effective in the management of temporal lobe seizures we found that only primidone and phenobarbital have not been convincingly associated with such side effects. However, phenytoin and clonazepam have been linked with urinary incontinence, and valproic acid with enuresis.

Adolescent