ADME & Pk/Pd measurements

Pharmacokinetics of Rivastigmine in blood

Rivastigmine, a reversible cholinesterase inhibitor, approved in the US and EU for the treatment of dementia due to Alzheimer’s disease or Parkinson’s disease, was suggested as pretreatment against nerve agent poisoning.

In order to evaluate side effects, behavior effects, pharmacokinetics (PK) & pharmacodinamics (PD) of Rivastigmine of healthy population, a clinical study was carried out. Fourteen healthy male volunteers have been assigned to randomly receive either placebo, 1.5mg or 3mg Rivastigmine for 5 consecutive times (every 12 hr.) P.O. by a cross over, double blind trial. A period of one week washout was placed between doses.

A sensitive bioanalytical method was developed for the determination of Rivastigmine pharmacokinetics in plasma samples. A rapid (cycle time = 11 min) and sensitive gas chromatography mass spectrometry (GC-MS) method was developed and validated for the quantitation of Rivastigmine in human plasma (LOQ = 0.2 ng/ml). Blood samples were collected and Rivastigmine was extracted from human plasma using liquid-liquid extraction (LLE) when deuterated Rivastigmine was used as the internal standard.

Pharmacokinetic profile