Pharmacokinetic and pharmacodynamic aspects of gastroretentive dosage forms

• Published in: International journal of pharmaceutics Vol. 277; no. 1; pp. 141 - 153
• Main Authors: Hoffman, Amnon, Stepensky, David, Lavy, Eran, Eyal, Sara, Klausner, Eytan, Friedman, Michael
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 11.06.2004; Elsevier
• Subjects: Animals; Bioavailability; Biological and medical sciences; Controlled release; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - metabolism; Gastroretentive dosage forms; General pharmacology; Humans; Levodopa; Medical sciences; Metformin; Pharmaceutical technology. Pharmaceutical industry; Pharmacodynamics; Pharmacokinetics; Pharmacology. Drug treatments; Riboflavin; Pharmacodynamics; Riboflavin; Bioavailability; Metformin; Levodopa; Pharmacokinetics; Controlled release; Gastroretentive dosage forms; Delivery system; Stomach; Pharmaceutical technology; Residence time; Controlled release form; Vitamin; Oral administration; Hypoglycemic agent; Biguanides; Levedepe Riboflavin; Controlled release: Bioavailability
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2003.09.047

Controlled release gastroretentive dosage forms (CR-GRDF) enable prolonged and continuous input of the drug to the upper parts of the gastrointestinal (GI) tract and improve the bioavailability of medications that are characterized by a narrow absorption window. CR-GRDF provide a means to utilize all the pharmacokinetic (PK) and pharmacodynamic (PD) advantages of controlled release dosage forms for such drugs. Thus, CR-GRDF may improve therapy with clinically used medications, as well as enable oral administration of drugs, or drug candidates, that hitherto had to be infused parenterally. This manuscript discusses the complexity of the PK and PD factors that influence the treatment benefits of CR-GRDF and summarizes the results of our recent in vivo investigations in animal models (rats and dogs) and in human subjects. We found that a CR-GRDF formulation was superior to the other modes of administration for levodopa and riboflavin, but not for metformin. The PK and PD rationales of GRDFs for the studied drugs are presented and discussed. We conclude that due to the complexity of the PK and PD factors for a certain drug, the rationale for continuous administration obtained by CR-GRDF should be assessed and established in vivo.