Abstract
The equation log(concentration) = a + b/ [Formula: see text] + c· [Formula: see text] + d·(T − φ) was used to calculate serum level curves from individual data sets of drug serum concentrations, obtained from experiments with orally administered drugs. These curves were subsequently used to calculate peak values, times for onset of peak, area, and other pharmacokinetic parameters that ought to be independent of any preconceived theory about the behavior of the drug in the system. A program is described by which parameters for individual data sets can be calculated and a mean curve with a peak value, time for onset of peak, and area equal to the arithmetic mean of the corresponding values for the participating subjects, is produced. The results of this method are compared to those of the “one-compartment model with lag time” and shown to be superior in all the test cases. In particular, the proposed method performs well with data from a highly protein-bound drug, for which the one-compartment model fails completely. Data sets of six to eight samples taken over the entire period of detectable serum levels, with 10% analytical error in the results, gave estimates of peak value and area with a coefficient of variation of 6 to 9%, whereas the variation in the estimates for different subjects in a treatment group amounted to 20 to 60%. This shows that the proposed method, although able to cope with a short series of imprecise measurements available in practical work, is still sufficiently sensitive to detect real differences between the individual subjects.
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Selected References
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- Knothe H., Lauer B., Fabricius K. Ampicillin, Pivampicillin und Amoxicillin. Vergleichende Untersuchungen von Serumkonzentrationen und Urinausscheidung nach oraler Nüchterngabe. Arzneimittelforschung. 1974 Jun;24(6):951–955. [PubMed] [Google Scholar]
- Leeson L. J., Weintraub H. Calculating absorption rate constants for drugs with incomplete availability. J Pharm Sci. 1973 Dec;62(12):1936–1941. doi: 10.1002/jps.2600621206. [DOI] [PubMed] [Google Scholar]