Abstract
The urinary excretion rates of methaqualone and of one of its metabolites, 6-hydroxymethaqualone (free and conjugated), were determined in a normal male subject over a 30-day period by stable isotope dilution analysis using field ionization mass spectrometry. The excretion rates for methaqualone were fitted by computer to three-and four-exponential functions. The estimated terminal halflife for the drug was approximately 74 hr. 6-Hydroxymethaqualone excretion in the elimination phase was fitted to a single exponential decay curve. Estimated halflives obtained for the free and total (primarily conjugated) metabolite were 78 and 70 hr, respectively. The apparent difference between the latter two values was not statistically significant. The close similarity between the halflives of methaqualone and 6-hydroxymethaqualone indicates that elimination of these compounds is ratelimited by the same pharmacokinetic process. A similarly long halflife, 50 hr, was estimated in a previous study (5) of another subject in which excretion of the compounds was followed over an 11-day period. These results demonstrate that the half-life of methaqualone can be much longer than has been indicated by relatively short-term investigations.
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M. Gibaldi and H. Weintraub. Some considerations as to the determination and significance of biologic half-life.J. Pharm. Sci. 60:624–626 (1971).
R. K. Nayak, R. D. Smyth, J. H. Chamberlain, A. Polk, A. F. DeLong, T. Herczeg, P. B. Chemburkar, R. S. Joslin, and N. H. Reavey-Cantwell. Methaqualone pharmacokinetics after single-and multiple-dose administration in man.J. Pharmacokin. Biopharm. 2:107–121 (1974).
J. M. Clifford, J. H. Cookson, and P. E. Wickham. Absorption and clearance of secobarbital, heptabarbital, methaqualone, and ethinimate.Clin. Pharmacol. Ther. 16:376–389 (1974).
G. Alván, J. E. Lindgren, C. Bogentoft, and Ö. Ericsson. Plasma kinetics of methaqualone in man after single oral doses.Eur. J. Clin. Pharmacol. 6:187–190 (1973).
J. H. McReynolds, H. d'A. Heck, and M. Anbar. Determination of picomole quantities of methaqualone and 6-hydroxymethaqualone in urine.Biomed. Mass Spectrom. 2:299–303 (1975).
J. G. Wagner. Some possible errors in the plotting and interpretation of semilogarithmic plots of blood level and urinary excretion data.J. Pharm. Sci. 52:1097–1101 (1963).
J. G. Wagner.Fundamentals of Clinical Pharmacokinetics, Drug Intelligence Publications, Hamilton Press, Hamilton, Ill., 1975, pp. 102–106.
J. G. Wagner.Fundamentals of Clinical Pharmacokinetics, Drug Intelligence Publications, Hamilton Press Hamilton, Ill., 1975, pp. 114–119.
H. G. Boxenbaum, S. Riegelman, and R. M. Elashoff. Statistical estimations in pharmacokinetics.J. Pharmacokin. Biopharm. 2:123–148 (1974).
R. L. Wine.Statistics for Scientists and Engineers, Prentice-Hall, Englewood Cliffs, N.J., 1964, pp. 508–510.
Fr. R. Preuss, H. M. Hassler, and R. Köpf. Zur Biotransformation des 2-Methyl-3-o-tolyl-4(3H)-chinazolinon (=Methaqualon).Arzneimittel-Forsch. 16:395–401 (1966).
R. Bonnichsen, Y. Mårde, and R. Ryhage. Identification of free and conjugated metabolites of methaqualone by gas chromatograpny-mass spectrometry.Clin. Chem. 20:230–235 (1974).
A. Polk, A. F. DeLong, R. D. Smith, T. Herczeg, B. J. Burns, L. J. Klunk, Jr., and N. H. Reavey-Cantwell. Biliary excretion and enterohepatic recirculation of methaqualone in the rat.Drug Metab. Dispos. 2:365–369 (1974).
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Supported by Contract DADA17-73-C-3063 from the U.S. Army Medical Research and Development Command.
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Heck, H.A., Maloney, K. & Anbar, M. Long-term urinary excretion of methaqualone in a human subject. Journal of Pharmacokinetics and Biopharmaceutics 6, 111–122 (1978). https://doi.org/10.1007/BF01117446
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DOI: https://doi.org/10.1007/BF01117446