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Pharmacokinetics of ketotiffn after oral administration to healthy male subjects
Author(s) -
Grahnén A.,
Lönnebo A.,
Beck O.,
Eckernäs SÅ,
Dahlström B.,
Lindström B.
Publication year - 1992
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510130404
Subject(s) - ketotifen , pharmacokinetics , dosage form , capsule , medicine , oral administration , absorption (acoustics) , pharmacology , botany , physics , asthma , acoustics , biology
The pharmacokinetics of 2 mg ketotifen from four different oral dosage forms were examined in two randomized, balanced cross‐over studies. Forty healthy male subjects participated. Each of 20 subjects received two capsule formulations and each of the other 20 subjects received two syrup formulations. Ketotifen concentrations in plasma were determined by a modified GC—MS method. The limit of quantitation was 40 pg ml −1 . Inter‐day precision and accuracy calculated from quality control samples were 16·3 per cent (−1·9 per cent), 19·8 per cent (+4·5 per cent) and 23·6 per cent (+ 5·9 per cent) at plasma concentration levels of 86 ( n = 18), 215 ( n = 19) and 343 ( n = 18) pg ml −1 , respectively. Ketotifen was rapidly absorbed from all dosage forms reaching C max in the order of 400 pg ml −1 after the syrup formulations and 300 pg ml −1 after the capsule formulations within 2 to 4 h. The syrup formulations showed a significantly more rapid rate of absorption as assessed by T max . No significant differences in extent of absorption between dosage forms were observed. The terminal elimination half‐life of ketotifen varied between subjects from 7 to 27 hours with a mean of about 12 h. The minor pharmacokinetic difference between dosage forms observed in this study is unlikely to be of clinical significance.