Pharmacokinetics of ketotiffn after oral administration to healthy male subjects

Abstract

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 Cmax 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 Tmax. 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.

A Class of Tricyclic Compounds Blocking Malaria Parasite Oocyst Development and Transmission

“…Large doses have been tested in rats and rabbits with minimum side effects, including during pregnancy. Ketotifen is well absorbed after oral administration, with peak plasma drug concentrations within 2 to 4 h. Peak plasma drug concentrations after multiple oral doses of 1 mg twice daily were 1.92 mg/liter in adults and 3.25 mg/liter in children (41). The drug is 75% protein bound and is metabolized in the liver to the inactive form, ketotifen-N-glucoronide, and active norketotifen.…”

Determination of some antiallergic drugs in human plasma by direct-injection high-performance liquid chromatography-tandem mass spectrometry

“…Many methods have been reported for the determination of antiallergic drugs in various matrices by GC-MS [18,19], HPLC with UV detection [20,21], HPLC-MS [22], and HPLC-MS-MS [23][24][25][26]. In most of the above methods, the off-line extraction such as LLE [22,24] or SPE [19,23,25,26] had been used for removal of impurities contained in human plasma or serum.…”

Determination of ketotifen in human plasma by LC–MS

“…1). The glucuronide conjugate and the N-oxide ketotifen readily undergo hydrolysis to parent drug by ␤-glururonidase [2][3][4][5][6][7][8][9]. Preclinical studies indicated that ketotifen's anti-H1 effect seems to be distinct from its anti-allergic properties.…”