Therapeutic drug monitoring
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The use of phenytoin has increased among the rural black population in South Africa, many of whom have albumin concentrations below the accepted reference range of 35-50 g/L, related to a combination of malnutrition and late-presenting renal and hepatic disease. Because albumin concentration has a major effect on the proportion of free phenytoin in the extracellular fluid, we instituted a study of the extent of hypoalbuminemia and of the difference between "total" phenytoin (measured by immunoassay), and "corrected" phenytoin (calculated using the Sheiner-Tozer equation, which is based on a mean albumin of 40 g/L). The differences were significant (higher than 20%) in 37% of patients and led us to propose that in populations in which there is a high proportion of patients who are hypoalbuminemic, it is corrected rather than total phenytoin that should be the value reported.
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Randomized Controlled Trial Clinical Trial
Spectral analysis of heart rate variability as a quantitative measure of parasympatholytic effect--integrated pharmacokinetics and pharmacodynamics of three anticholinergic drugs.
The time course and concentration-effect relationship of parasympatholytic effects of three anticholinergic drugs were investigated using spectral analysis of heart rate (HR) variability. Single intravenous (i.v.) doses of atropine (10 microg/kg), glycopyrrolate (5 microg/kg), scopolamine (5 microg/kg), and placebo were given to eight healthy volunteers in a double-blind, randomized cross-over study. Electrocardiogram (ECG) was recorded at baseline and 2.5, 5, 10, 20, and 30 minutes, and 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration, while the subjects breathed at a fixed 0.25 Hz frequency. ⋯ Spectral analysis of HR variability appears to be a powerful tool in monitoring parasympatholytic drug activity. A sigmoidal Emax model with an extremely steep concentration-response relationship was revealed for atropine and glycopyrrolate. The effects of scopolamine were more incongruous.
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Clinical Trial Controlled Clinical Trial
The influence of the route of administration: a comparative study at steady state of oral sustained release morphine and morphine sulfate suppositories.
Steady state pharmacokinetics of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were investigated in 6 patients with intractable cancer pain administered orally with MST (Mundipharma, Limburg, Germany) and, subsequently, rectally with MSR to make a judgment whether orally administered morphine can be replaced by rectally administered morphine. The parent drug and glucuronide metabolites were measured simultaneously using high-performance liquid chromatography (HPLC) and native fluorescence detection. The mean morphine area under the curve (AUC) value (0-8 h) was smaller (434.3 +/- 170.2 nmolL(-1)h) in the oral administration than in the rectal administration (574.8 +/- 285.0 nmolL(-1)h) (p < 0.05). ⋯ Four of the 6 patients had a greater Cmax of M3G and M6G after oral administration than after rectal administration. The same 4 had lower fluctuation rates for morphine, M3G (p < 0.05), and M6G (p < 0.05) after rectal administration. Therefore, during chronic morphine treatment, it still seems difficult to decide whether oral administration can be replaced by rectal administration.