Moments analysis has been applied to the calculation of mean (in vivo)dissolution time (MDT) and mean absorption time (MAT) from plasma level of drug versus time data. Methods for accurately estimating the MDT under varying conditions, limitations of the methods, and interpretation of the data are presented. The importance of accurate estimates of the terminal rate constant (λ z) and the drug concentration at the time of withdrawing the final plasma sample (Ĉz)is emphasized in connection with extrapolation to t=∞.The appropriate use of a logarithmic trapezoidal equation for calculating the area under the moments curve (AUMC) is shown to increase the accuracy of estimating MDT.
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K. Yamaoka, T. Nakagawa, and T. Uno. Statistical moments in pharmacokinetics.J. Pharmacokin. Biopharm. 6:547–558 (1978).
D. J. Cutler. Theory of the mean absorption time, an adjunct to conventional bioavailability studies.J. Pharm. Pharmacol. 30:476–478 (1978).
H. F. Martin, B. J. Gudzenowicz, and H. Fanger.Normal Values in Clinical Chemistry, a Guide to Statistical Analysis of Laboratory Data, Marcel Dekker, New York, 1975, pp. 167–170.
L. Z. Benet and R. L. Galeazzi. Noncompartmental determination of the steady state volume of distribution.J. Pharm. Sci. 68:1071–1074 (1979).
W. Perl and P. Samuel. Input-output analysis for total input rate and total traced mass of body cholesterol in man.Circ. Res. 25:191–199 (1969).
J. H. Oppenheimer, H. L. Schwartz, M. I. Surks. Determination of common parameters of iodothyronine metabolism and distribution in man: noncompartmental analysis.J. Clin. Endocrinol. Metab. 41:319–324 (1975).
D. M. Himmelblau and K. B. Bischoff.Process Simulation in Determination Systems, Wiley, New York, 1968.
R. A. Shipley and R. E. Clark.Tracer Methods for In Vivo Kinetics. Theory and Applications, Academic, New York, 1972.
M. Rowlandet al. Scientific commentary on mathematical symbols,J. Pharmacokin. Biopharm. 8:421 (1980).
J. G. Wagner and coworkers. Pharmacokinetic parameters estimated from intravenous data by uniform methods and some of their uses.J. Pharmacokin. Biopharm. 5:161–182 (1977).
W. Weibull. A statistical distribution function of wide applicability.J. Appl. Mech. 18:293–297 (1951).
F. Langenbucher. Linearization of dissolution rate curves by the Weibull function.J. Pharm. Pharmacol. 24:979–981 (1972).
S. Riegelman and R. Upton. Studies onin vitro andin vivo drug release correlations. In L. F. Prescott and W. S. Nimmo (eds.),Drug Absorption—Proceedings of Edinburgh International Conference, ADIS Press, New York, 1980.
J. A. Clements, R. C. Heading, W. S. Nimmo, and L. F. Prescott. Kinetics of acetaminophen and gastric emptying in man.Clin. Pharmacol. Ther. 24:420–431 (1978).
Federal Register—Part 320 Tricylic Antidepressants.43(34):6965–6969 (February 17, 1978).
Federal Register—Part 320 Certain Anticonvulsants.42(151):39675–39679 (August 5, 1977).
U.S. Food and Drug Administration Division of Biopharmaceutics. “Guidelines forin vivo bioavailability studies for chlorthalidone diuretics” (1979).
W. L. Chiou and S. Riegelman. Disposition kinetics of griseofulvin in dogs.J. Pharm. Sci. 58:1500–1504 (1969).
M. Gibaldi and D. Perrier.Pharmacokinetics, Marcel Dekker, New York, 1975, pp. 267–279.
P. A. McCollum and B. F. Brown.Laplace Transform Tables and Theorems, Holt, Rinehart and Winston, New York, 1965, pp. 65–76.
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Riegelman, S., Collier, P. The application of statistical moment theory to the evaluation ofin vivo dissolution time and absorption time. Journal of Pharmacokinetics and Biopharmaceutics 8, 509–534 (1980). https://doi.org/10.1007/BF01059549
- mean dissolution timein vivo