A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Clinical significance of SNAP somnography test acoustic recording.

OBJECTIVE: To examine the clinical significance of acoustic data recorded by the SNAP home polysomnography system (SNAP Laboratories, Glenview, IL). STUDY DESIGN AND SETTING: Retrospective analysis of SNAP data from 59 patients undergoing evaluation for sleep apnea at the University of Nebraska Medical Center and an associated private practice in Omaha, NE. RESULTS: Snoring did not correlate with anthropometric variables such as body mass index and neck circumference. Statistical analysis showed no correlation between respiratory disturbance index and the maximum or average loudness of snoring. Average loudness was predictive of the presence of sleep apnea. Spectral analysis of snoring sonography found that the proportion of snoring events associated with a palatal source correlated strongly with the loudness of snoring. CONCLUSION: These data suggest that analysis of snoring has limited utility in the evaluation of the patient with sleep apnea but may be able to select patients who would benefit from palatal procedures to reduce snoring.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.     

Internal fixation for occipito-cervical fusion

We describe a method of internal fixation for occipito-cervical fusion utilising a standard "small fragment" T-plate bent and fixed to the skull with three screws. The lower end of the plate is screwed and wired firmly to the spine of the axis. Of 14 patients so treated, 12 fused, one died and one failed to unite to the skull. Of eight with cord signs, seven remitted or improved and one died.     

A disorder of lightness discrimination in a case of visual form agnosia

Benson and Greenberg (1969) described an "agnosic" patient whose severe visual recognition disorder could be accounted for in terms of a deficit in the perception of shape. We report here on a recent case of this disorder (visual form agnosia), and have found that she performs very poorly on tasks of discriminating shades of grey, although she is able to discriminate between hues. This sensory deficit helps to explain some of her perceptual difficulties; it also provides further evidence for parallel feature-processing in the human brain complementary to and consistent with recent physiological data on the visual cortex in animals.