Pharmacokinetics of oral noscapine.
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.
Karlsson
M O
MO
Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, Uppsala University, Sweden.
Dahlström
B
B
Eckernäs
S A
SA
Johansson
M
M
Alm
A T
AT
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D008297:Male; D009665:Noscapine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011897:Random Allocation; D012996:Solutions; D013607:Tablets
D012996:Solutions; D013607:Tablets; D009665:Noscapine