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  • bioavailability  (2)
  • Springer  (2)
  • American Chemical Society
  • 1980-1984  (2)
  • 1950-1954
  • 1945-1949
  • 1880-1889
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  • Springer  (2)
  • American Chemical Society
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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of zimelidine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    Details
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562618
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  • 2
    Electronic Resource
    Electronic Resource
    Bioavailability of microsize and ultramicrosize griseofulvin products in man (1980)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 347-362 
    Details
    ISSN: 1573-8744
    Keywords: griseofulvin ; bioavailability ; HPLC assay ; plasma levels ; human study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The relative bioavailability of ten marketed dosage forms of griseofulvin was evaluated in two separate crossover studies. Each study utilized 12 healthy subjects, with eight of the subjects being common to both studies. Plasma griseofulvin concentrations were determined 1, 2, 3, 4, 6, 8, 10, 25, 34, 49, and 73 hr after dosing, using a high-pressure liquid chromatographic method. The “high-dose” study compared four microsize dosage forms administered as 500-mg doses and two ultramicrosize formulations given as 250-mg doses. The “low-dose” study employed four 250-mg microsize products and two 125-mg ultramicrosize products. The individual plasma level-time profiles for the majority of doses suggested prolonged absorption of microsize griseofulvin. The ultramicrosize dosage forms exhibited peak concentrations which were not significantly different (p〉0.05) from those of the microsize products administered as twice the dose. In the high-dose study, the two 250-mg ultramicrosize dosage forms exhibited areas under the plasma level-time curve (AUC) which were significantly (p〈0.05) less than the AUCs for all but one of the 500-mg microsize products. In the low-dose study the AUCs for the ultramicrosize products were significantly lower than the AUCs for all of the microsize dosage forms. Significant differences were also noted among the AUCs for the microsize products, although the maximum difference was less than 20% in both studies. A comparison of the AUCs observed in the high- and low-dose studies revealed that the AUCs for two of the 500-mg microsize dosage forms were only approximately 75% the AUC predicted from the 250-mg dose for the eight subjects common to both studies. All other formulations exhibited a dose proportionality for AUC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059383
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