Biomedical subjects
Publications and source records attributed to T B Cooper.
The authors describe a technique that enables a physician to determine individual patient dosage requirements for nortriptyline from a single 24-hour blood sample. Because the technique reveals immediately those patients at the extremes of dosage ranges, toxicity and the need for time-consuming titration of the dosage regimen can be avoided.
A slow-release lithium preparation was compared with a standard formulation in normal volunteers and in patients. Pharmacokinetic parameters of normal volunteers were examined after a single dose of each form and the steady-state levels after a b.i.d. dose of the slow-release form. These initial single-dose data suggested that the two formulations are not bioequivalent. However, the area under the curve of the two forms was similar, and the essentially complete recovery of lithium from urine in steady state indicates equal bioavailability. The patients' steady-state levels for the two formulations essentially confirmed the normal subjects' data: with the slow-release form plasma lithium levels were slightly higher, and the postdose lithium level variability was decreased by as much as 50%.
We retrospectively assessed our experience with the use of bipolar atrial epicardial electrodes in 70 consecutive patients following open-heart surgery. These patients, representing 1 month's experience on one of our cardiac surgical services, are a random sample of our total experience with more than 6.000 patients in whom we have routinely placed such electrodes. The atrial wire electrodes were used diagnostically and/or therapeutically in 57 patients a total of 139 times. In only 13 patients were the atrial wires not used for any reason. Atrial electrograms were recorded 63 times in 34 patients, 41 times to establish a diagnosis of an arrhythmia and 22 times to confirm the diagnosis of an arrhythmia originally suspected from interpretation of a standard or monitor electrocardiogram (ECG). Atrial pacing was used to treat abnormalities of rhythm or conduction or both in 75 instances in 49 of the 70 patients. Because of their great utility in the diagnosis and treatment of arrhythmias, we conclude that routine placement of atrial wire electrodes at the time of operation is indicated regardless of the nature of the open-heart procedure or the preoperative rhythm.
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Older depressed patients treated with imipramine or amitriptyline developed higher steady-state plasma levels of imipramine, desipramine, and amitriptyline. In imipramine-treated patients this finding was associated with a decreased rate of drug elimination from plasma. These findings provide at least a partial explanation for the increased susceptibility of the older patient to tricyclic antidepressant side effects and also provide a pharmacological rationale for use of lower dosages in this age group.
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The authors have previously described a technique whereby individual lithium dosage requirements can be predicted from 24-hour blood samples. Further experience over a 2-year period has shown the predictions to be reproducible over time. A micromethod for lithium determination is described, as are several cases in which aberrant results were found to indicate inadequate laboratory techniques or patients' failure to take medication. Because the technique reveals immediately those patients at the extremes of dosage ranges, toxicity and the need for frequent sampling can be avoided.
A highly sensitive and reproducible GLC technique for the quantitation of amitriptyline and nortriptyline is described. The lower limit of detection is less than 1 ng/ml. 5 ng/ml samples (3 ml aliquots) can be accurately quantified (C of V less than 5%). Steady state data are reported together with data on amitriptyline and nortriptyline levels obtained in a volunteer who ingested a single oral dose (25 mg) of amitriptyline (Elavil).
Experimental evidence showed that a higher whole blood steady state drug plasma level was achieved when a patient was given medication three times a day compared to the same total daily dose once a day. In addition, evidence indicated possible enzyme induction by butaperazine in one patient. We have demonstrated that the general stochastic theory developed to investigate the pharmacokinetics of lithium carbonate "in vivo" has more general applicability in that it applies also to butaperazine, and facilitates interpretation of findings (without blood level data) in one other drug study.
Various aspects of iodine metabolism were studied in adult beagles maintained at iodine intake levels ranging from 480 to 20 mug/day. On the basis of changes in radioiodine metabolism, the minimum daily iodine requirement of the adult beagle was found to be 140 mug. Although striking changes were observed in radioiodine metabolism when iodine intake was reduced to 90mug/day, serum T4 and T3 levels were unaffected. Marked reductions in serum T4 occurred in dogs restricted to an iodine intake of 50 or 20 mug/day, but even at these low levels of iodine intake there were only slight reductions in serum T3 concentration and a eumetabolic state was maintained. Prolonged iodine deficiency (8-12 months) resulted in variable patterns of thyroid histology, which were related to differences in thyroidal 127I content and in the rate of release of radioiodine from the thyroid. The heterogeneity in thyroid morphology and iodine kinetics did not, however, have a significant effect on serum T4 and T3 levels.
A sensitive method for determination of imipramine and desmethylimipramine using a GLC system fitted with a new nitrogen detector is described. The lower limit of sensitivity is less than 1 ng/ml with a lower limit enabling quantitation with acceptable precision of 3-5 ng/ml. Data from 20 control subjects given a single oral dose of imipramine are shown.
Preliminary observations in a small animal sample reveal that chronic lithium treatment in rats produced significant changes in the microvillous processes on the cell surface of the choroid plexus. These alterations may be associated with increased intracellular choroidal volume. The type of changes noted by SEM suggest an alteration in movement of water into the extracellular areas of the brain. This basic alteration produced by lithium in the secretory/absorptive capacity of the chorid plexus is probably reversible.
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