Pharmacokinetic Studies Of Chronopharmaceutical, Conventional And Pure Drug Delivery System Of Theophylline By LC-MS/MS Method

Clinical studies have shown that circadian patterns influence the pharmacokinetics of certain drugs used in the treatment of different diseases. For such drugs, the bioavailability is influenced by the time of administration. The objective of this study was to investigate differences in the pharmacokinetic patterns between a pulsatile drug delivery system using a pulsatile capsule, pure active pharmaceutical ingredient (theophylline) and an exisisting marketed immediate release tablet (conventional). Theophylline was chosen as a model drug because of its significant solubility and permeability pattern throughout the GI tract. The dosage form of 400 mg each were administered to 3 groups of white New Zealand rabbits (n=6) following cross over design pattern and the plasma levels were measured using LC-MS/MS method. Pharmacokinetic parameters were determined for each dosage form. The comparison of the plasma time curves of the dosage forms showed that each dosage form caused significant differences in the drug plasma levels. The plasma drug profiles of active pharmaceutical ingredient and marketed conventional tablet of theophylline showed nearly similar pattern of drug release, whereas the pulsatile capsular formulation prepared in the laboratory managed to show some lag phase initially before releasing the drug. The pulsatile drug delivery capsule showed maximum time (Tmax) at the 8 hour in comaprision to active ingredient which showed plasma peak in the range of 2-3 hours. Implications for the use of a pulsatile drug delivery device for chronopharmacotherapy are discussed. Pulsatile drug delivery offers a promising way for chronopharmacotherapy if the time of administration and pulse time are adjusted to the circadian pattern.