Biomedical subjects
P Goldenheim
Publications and source records attributed to P Goldenheim.
Controlled-release morphine bioavailability (MS Contin tablets) in the presence and absence of food.
The bioavailability of a single, orally administered, 30-mg controlled-release morphine tablet (MS Contin Tablet; The Purdue Frederick Company, Norwalk, Conn.) was compared after fasting or a high fat meal in this single dose, randomized, crossover study involving 24 healthy male subjects. There was no significant (p greater than 0.05) difference in the mean extent of morphine absorption over 24 hours in the presence or absence of food (area under the plasma concentration vs. time curve [AUC(0,24)], fed = 107% of fasted). Time to maximal concentration (Tmax) was similar (p greater than 0.05) in the two treatment groups; the mean Tmax for fed volunteers was 2.5 hours versus 2.4 hours for fasted volunteers. The two regimens did not differ significantly (p greater than 0.05) with regard to maximal morphine concentration (Cmax); mean Cmax for fed subjects was 8.22 ng/ml whereas mean Cmax for fasted subjects was 8.53 ng/ It was concluded that consumption of a high fat meal did not affect either the rate or extent of morphine absorption, or any of the other pharmacokinetic parameters tested, following administration of MSC.
Evaluation of a cancer pain model for the testing of long-acting analgesics. The effect of MS Contin in a double-blind, randomized crossover design.
A double-blind, double-dummy, crossover study compared oral controlled-release morphine sulfate (MS Contin tablets [MSC], Purdue Frederick, Norwalk, CT) every 12 hours, and immediate-release morphine sulfate (IRMS) tablets, every 4 hours, in 14 evaluable patients with chronic cancer pain. The test model described showed assay sensitivity for steady-state analgesia, requiring relatively few subjects to yield statistical significance in pharmacologic potency estimates. Initial doses were the calculated equivalents of about one third the previous opioid requirements or at least 30 mg MSC every 12 hours or 15 mg IRMS every 4 hours. This was generally subtherapeutic; hence, additional IRMS was available for break-through pain. Doses of MSC and IRMS were titrated upwards until the requirement for rescue IRMS was less than 20% of the total daily amount of morphine. In both study phases, the total dose of morphine increased significantly from the first day to the last, on which it was significantly (34%) higher for IRMS than MSC. Pain was significantly less intense and frequent in the last 24 hours of each treatment arm than in the first, and equally well controlled by both regimens. The two treatments were equipotent in a pharmacologic assay using dosages and pain scores. The requirement for rescue analgesia was similarly comparable for both treatments, decreasing significantly with upward dose titration. The few side effects experienced (one with MSC and three with IRMS) did not include serious reactions such as respiratory depression. It is concluded that MSC, 12-hourly, controls cancer pain as effectively and safely as IRMS on a 4-hour schedule. MS Contin exhibits a 12-hour duration of action as previously shown in other well-controlled trials. A problem of pain exacerbation at the start of each study phase was found to be associated with the design of this study. It may be resolved with a higher initial study dose and/or use of a patient-controlled analgesia device for parenteral rescue doses.
Noninvasive testing of asymptomatic bilateral hilar adenopathy.
The diagnostic strategy for asymptomatic patients with persistent bilateral bilar adenopathy often involves invasive procedures. The authors used Bayesian analysis to: 1) estimate the relative prevalences of diseases causing bilateral bilar adenopathy; 2) assess changes in the prevalence of disease by race, the presence of other clinical symptoms, and geography; and 3) determine the value of relevant noninvasive tests, including the angiotensin-converting enzyme (ACE) assay, gallium scan, and purified protein derivative (PPD), in order to assess when a strategy of watchful waiting is appropriate. The analysis indicated that the ACE assay, particularly when paired with the PPD, can identify many patients who might safely be managed without immediate invasive biopsy. Patients who are ACE+ and PPD- have an estimated probability of sarcoidosis of 0.95 or greater; patients who are ACE- and PPD+ have a probability of tuberculosis of 0.86 if black, 0.79 if white. In contrast, gallium scanning has no diagnostic role in this clinical situation. Bronchoscopic or mediastinoscopic biopsy has a limited role for patients who are ACE+ PPD- or ACE- PPD+ because of limited sensitivity. Patients who are both ACE- and PPD-, particularly if white, may have a high enough risk of lymphoma to consider invasive biopsy.