ISSN:
1432-1041
Keywords:
Noscapine
;
pharmacokinetics
;
bioavailability
;
dose dependency
;
oral administration
;
inter- and intra-individual variability
;
adverse events
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The relative bioavailability in 20 healthy volunteers of 100 mg, 200 mg and 300 mg tablets of noscapine and 200 mg as a solution has been assessed in a four-way cross-over study, with repeated administration of the 200 mg dose to assess intraindividual variability. There was a disproportionate increase in the AUC of noscapine tablets, as a 3-fold increase in dose produced a 9-fold rise in AUC. This dose-dependency could mainly be attributed to saturable first-pass metabolism of the drug. Administration of noscapine as a solution resulted in a significantly higher maximal concentration at an earlier time-point and a higher AUC than the corresponding dose as tablets. Repeated administration of noscapine tablets and solution yielded higher AUC on the second dosing occasion. No cause for this carry-over effect was found, and the contribution of remaining noscapine was negligible. The terminal half-life of noscapine, which was independent of formulation or dose size was 4.5 h. Both inter- and intraindividual variability in noscapine kinetics were very high, e.g. 73% and 51% CV of the AUC for the 200 mg tablet.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00315110
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