Three novel colorimetric methods of detecting urinary nicotine metabolites called the barbituric acid, diethylthiobarbituric acid (DETB), and DETB extraction methods were evaluated for use as a simple, cheap, objective test of smoking. Urine samples were collected from 103 male smokers and 78 male non-smokers working at two London factories. The smokers recorded the number of cigarettes smoked over the previous 36 hours. All three methods correctly classified the smokers. The DETB extraction method had a lower false positive rate (averaging 3% on morning and afternoon urine samples) than either the DETB or the barbituric acid method (12% and 6% respectively) and was the best procedure for classifying subjects as "smokers" or "non-smokers." When a quantitative variant of the barbituric acid method was used there was a significant correlation (r = 0.85, p < 0.001) between the ratios of urinary nicotine metabolites to creatinine and the number of cigarettes smoked. The ratios for smokers of 6-15, 16-25, and 26 or more cigarettes, however, overlapped considerably. The methods can be performed very rapidly and the reagent cost is equivalent to less than lp per test.
1. The possibility of using minute doses of the antituberculosis drug isoniazid (INH) or of its metabolites acetylisoniazid (AcINH) or isonicotinic acid (INA) as innocuous markers for monitoring patient compliance has been investigated. 2. The ingestion of these colourless and tasteless compounds can readily be demonstrated using a sensitive and specific colorimetric method for detecting INA and its metabolite isonicotinylglycine (INAG) in the urine that is rapid and simple to perform. 3. Studies on the kinetics of the urinary elimination of INA and INAG after the ingestion of 6 mg doses of either INH, AcINH or INA by small groups of volunteers indicated the potential suitability of INH or AcINH for monitoring daily or twice-daily self-medication and the appropriateness of INA as a marker for investigating the compliance of drugs prescribed for thrice-daily ingestion. 4. More extensive studies showed that over 99% of the urine samples collected within 18h of dosage with 6 mg INH would give positive results when tested for the presence of INA and INAG, and that doses of 2-6 mg INH could readily by incorporated into capsules or tablets and used as markers for monitoring the ingestion of the antituberculosis or antileprosy drugs dapsone, thiacetazone, ethionamide or prothionamide, or the antihypertensive oxprenolol. Such doses are less than a fiftieth of the normal therapeutic INH dose used in the treatment of tuberculosis. 5. Evidence is presented that INH, AcINH and INA possess most of the characteristics that one would hope to find in a marker for monitoring compliance including very limited inter-individual variability in the rates at which they are converted to the compounds being detected in the urine.
The pharmacokinetics of thiacetazone, a bacteriostatic drug with both antituberculosis and antileprosy activity, have been studied in healthy volunteers and tuberculosis patients using a high pressure liquid chromatographic method. Urinary excretion of thiacetazone was measured over a period of7 days fo llowing the ingestion of a single oral dose of 150 mg of the drug. Peak plasma concentrations of thiacetazone during supervised daily treatment averaged 1•8 Ilg/ml. From the rate of decline of thiacetazone plasma concentrations and urinary excretion, it was calculated that thiacetazone concentrations capable of inhibiting the multiplication of Mycobacterium /eprae would only be maintained for about 3 days in the event of patients discontinuing to take the drug. It was concluded that thiacetazone cannot be recommended for use in the multi-drug treatment of lepromatous leprosy.
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