RESUMO
Diacerein is a symptomatic slow-acting drug used for treating osteoarthritis. This drug is completely metabolized into the active metabolite rhein before reaching the systemic circulation. This study evaluated the effects of food on the pharmacokinetics of rhein released from diacerein in healthy Chinese subjects. This was a single-center, randomized, single-dose, open-label, two-period, cross-over study. Twenty-four healthy subjects were randomly selected to receive a single oral dose of 50 mg diacerein capsule in either fasted or fed state on two separate visits. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters were calculated using WinNonlin software. In the fasted and fed states, the main pharmacokinetic parameters of diacerein capsule were as follows: Cmax were (4471 ± 936), (3225 ± 755) ng/mL, t1/2 were (4.22 ± 0.42), (4.19 ± 1.05) h, tmax were (2.61 ± 1.25), (3.81 ± 1.29) h, AUC0-24 h were (24223 ± 4895), (24316 ± 5856) h·ng/mL, and AUC0-∞ were (24743 ± 5046), (25170 ± 6415) h·ng/mL. The absorption rate of diacerein capsule was obviously delayed by food intake but the absorption degree remained unaffected.
RESUMO
OBJECTIVE: To establish an LC-MS/MS method for the determination of levetiracetam to investigate the pharmacokinetics of levetiracetam extended-release tablets at fasted and fed states. METHODS: The separation was achieved on a Waters Symmetry C18 column (3.9 mm×150 mm, 5 μm) with mobile phase consisting of acetonitrile-5 mmol·L-1 ammonium acetate and 0.3% formic acid aqueous solution (10/90, V/V). Two subjects were randomly assigned to receive single oral dose of levetiracetam extended-release tablets 1 000 mg after being fasted and fed by a randomized crossover design. The plasma concentrations of levetiracetam were measured by LC-MS/MS. RESULTS: The calibration curve of levetiracetam in human plasma was linear over the concentration rang of 0.100 0-80.00 μg·mL-1. Under fasted and fed conditions, the main pharmacokinetic parameters of levetiracetam were as follows:ρmax were 20.50 and 19.09 μg·mL-1, AUC0-48 h were 345.4 and 336.3 μg·h·mL-1, tmax were 4.5 and 7.0 h, respectively. CONCLUSION: The method is proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetic study of 1 000 mg levetiracetam extended-release tablets in healthy Chinese volunteers after being fasted and fed. The result suggests that high fat and calories diet has effect on the pharmacokinetics of levetiracetam extended-release tablets, with tmax being delayed.