Rationale for apparent differences in pharmacokinetic aspects of model compounds determined from blood level data and urinary excretion data in rats
✍ Scribed by Yashwant M. Amin; Janardan B. Nagwekar
- Publisher
- John Wiley and Sons
- Year
- 1976
- Tongue
- English
- Weight
- 599 KB
- Volume
- 65
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
Results of studies carried out in rats for model compounds, D-(-)-mandelic acid, benzoylformic acid, and some of their para-alkylated homologs, showed that their biological half-lives determined from the elimination phase of urinary excretion data were longer than those determined from the elimination phase of blood level data. With compounds that followed multicompartment open models, the initial distributive phase (a-phase) noted from the blood level data was not detected from the urinary excretion data. Based on the analysis of half-life data obtained in the absence and presence of DL-tropic acid (a competitive renal tubular secretion inhibitor of these compounds), it is proposed that, besides the shortness of the a-phase period, the factor accounting for these striking differences in the pharmacokinetic aspects of these compounds is their retention and/or detention in the renal tubular membranes during their tubular secretion. Furthermore, it is proposed that the renal tubular membranes do not constitute a part of the central or peripheral compartment. Examples are cited to show that, where studies are reported for the same drugs in the same human subjects in the same laboratory, drugs usually exhibit longer biological half-lives when urinary excretion data rather than blood level data are used.
Keyphrases Pharmacokinetics-model compounds, urinary excretion and blood level data compared, rats 0 Elimination phase data-model compounds, urinary and blood level data compared, rats Biological half-lives-model compounds, determined from urinary excretion and blood level data and compared, rats