Outline Chapter 3

Physiochemical and Biopharmaceutical Properties of Drug substances and Pharmacokinetics Gastrointestinal PhysiologyBiologic membraneMechanisms of Drug Absorption Passive Diffusion Carrier-Mediated or Active Transport Convective Absorption  Ion-Pair AbsorptionPhysiochemical Factors Affecting Drug AbsorptionThe pH-Partition Hypothesis on Drug AbsorptionIonization and pH at Absorption Site Lipid Solubility   Partition Coefficient Estimation of Drug AbsorptionMeasurement of Permeability Cell Monolayer Biopharmaceutical Drug Classification  Class I Drugs (High Solubility and HIgh Permeability)  Class II Drugs (Low Solubility and HIgh Permeability)  Class III Drugs (High Solubility and Low Permeability)  Class IV Drugs (Low Solubility and Low Permeability)Role of Transporters in Drug Absorption Efflux TransportersProdrugs Strategic Considerations Type of Prodrugs  Hard Prodrug  Soft Prodrug  Carrier-Linked ProdrugMajor Objectives of Prodrug Design Improved Bioavailability Improved Aqueous Solubility Improved Passive Intestinal AbsorptionFactors Affecting the Absorption of Drugs from Solid Dosage Forms and SuspensionsDissolution pH and Solubility of Weak Acids and Bases Salts Solubility and Dissolution Rate Surface Area and Particle Size Polymorphism Estimate of Dose AbsorbedSummaryPharmacokineticsIntroductionCompartmental ConceptsLinear and Nonlinear Pharmacokinetics Linear PK Nonlinear PK Intravascular Administration  IV Bolus Administration and One-Compartment ModelElimination Rate Constant and Half-LifeApparent Volume of DistributionClearanceHepatic ClearanceIV Bolus Administration (Two-Compartment Model)Extravascular Route of AdministrationImportance of Absorption RateDetermination of Peak TimeDetermination of Peak Plasma ConcentrationsPeak Time and Peak Plasma ConcentrationBioavailabilityEstimating the Extent of Absorption Presystemic or First-Pass MetabolismRepetitive Drug Administration (Multiple Dosing)Plasma Protein Binding in PharmacokineticsStatistical Moment AnalysisSummary

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