Presentation on theme: "第二章 药物代谢动力学 Pharmacokinetics. Transformation Free Systemic Circulation Bound drug Free drug Metabolites Locus of Action “receptors” Bound Free Tissue."— Presentation transcript:
Transformation Free Systemic Circulation Bound drug Free drug Metabolites Locus of Action “receptors” Bound Free Tissue Reservoirs Bound Exceretion Absorption
Across membrane and lipid Across aqueous channel Carrier- mediated transport Outside Inside Manners of Transport Across Membrance Passive transport
Routes of Drug Administration Enteral within or by way of the GI tract Oral (PO), rectal, sublingual Parenteral Not within the alimentary canal Inhalation, IM, SC, IP, topical Central Into the brain or spinal cord Intrathecal
Routes of Drug Administration common abbreviations… PO = per os = oral IV = intravenous = into the vein IM = intramuscular = into the muscle SC = subcutaneous = between the skin and muscle IP = intraperitoneal = within the peritoneal cavity icv = intracerebroventricular = directly into the ventricle of the brain
Factors Affecting Response to Drugs Dosage Route of Administration Rate of Absorption Rate of Elimination Physiochemical properties of the drug age, sex, species, metabolism, etc…
Pharmacokinetic Evaluation of Gepirone Immediate-Release Capsules and Gepirone Extended-Release Tablets in Healthy Volunteers JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 9, SEPTEMBER 2003
Gepirone is a 5-HT 1A agonist for the treatment of major depression. half-life of 3 h and good oral bioavailability, and undergoes extensive first-pass metabolism
Because of its rapid absorption and short half-life, the gepirone-IR (immediate-release formulation) must be administered at least twice daily. This regimen results in high peak concentrations and marked peak-to- trough fluctuations in plasma concentrations.
These fluctuations may contribute to an increased incidence of adverse events, such as nausea, dizziness, headache, and somnolence, and have the potential to result in lower patient compliance and reduced effectiveness. extended-release gepirone formulation( ER ) immediate-release formulation(IR)
Figure 1. Mean gepirone plasma concentrations following administration of gepirone-IR formulations (10mgq12 h,n=12) or gepirone-ER formulations (ER-1: 20 mg q24 h, n=12; ER-2: 20 mg q24 h, n=12; ER-3: 25 mg q24 h, n=12).