The Influence of Routes of Administration on ADME Introduction Pharmacokinetics (PK) and Pharmacodynamics (PD) Toxicokinetics (TK) and Toxicodynamics (TD) Concepts Basic to PK and TK Influence of Routes of Exposure/Administration on PK/TK analysis Biomarkers References Mechanisms of Absorption and Permeation of Xenobiotics Introduction Passive Diffusion Carrier-Mediated Transcellular Diffusion Transcellular Diffusion Subject to P-Glycoprotein EffluxActive Transport Endocytosis and Pinocytosis Solvent Drag, Osmosis, and Two-Pore Theory Ion-Pair Absorption References In Vivo Distribution of Xenobiotics Introduction Factors Influencing the Distribution of Xenobiotics in the BodyReferences Elimination Rate, Clearance and the Theoretical Models Introduction Rate of Elimination and Extraction Ratio Clearance References Renal Excretion of Xenobiotics and Estimation of Related PK/TK Parameters and Constants Introduction Glomerular Filtration Tubular Reabsorption and Secretion Estimation of Glomerular Filtration Rate (GFR) Analysis of Urinary Data Renal Metabolism Estimation of PK/TK Parameters and Constants of Elimination When Using Dialysis References Biotransformation of Xenobiotics Introduction Liver Biotransformation (Metabolism) In Vitro Systems for Xenobiotics Metabolism Study In Vivo Samples for Drug Metabolism Study References Kinetics of In Vitro Metabolism Assimilation of Intrinsic Clearance in Hepatic Clearance Introduction Michaelis-Menten Kinetics Assimilation of Intrinsic Clearance in Hepatic Clearance Using Liver Models Inhibition of Xenobiotic Metabolism Induction of Xenobiotic Metabolism References Pharmaceutical, Biopharmaceutical, and Physiological Factors Influencing Oral Absorption of Xenobiotics-Mechanistic Absorption Models Introduction Classification of Factors Influencing GI Tract Absorption Mechanistic Absorption Models References Mathematical Modeling in Pharmacokinetics and Toxicokinetics Introduction Physiologically Based Pharmacokinetics Models (PBPK Models) Compartmental Analysis--Linear Pharmacokinetics Non-Compartmental Analysis Based on Statistical Moment Theory PK/PD and TK/TD Modeling Physiologically Based PK/PD or TK/TD Modeling Hysteresis Curve References PK/TK Analysis of Instantaneous Exposure to Xenobiotics (Single Bolus Injection) Introduction Linear One-Compartment Open Model Linear Two-Compartment Open Model with Elimination from the Central Compartment Linear Two-Compartment Open Model with Bolus Injection in the Central Compartment and Elimination from Peripheral Compartment Linear Three-Compartment Open Model with Bolus Injection and Elimination from Central Compartment Linear Three-Compartment Open Model with Elimination from Peripheral Compartment Comparing Models References PK/TK Analysis of Continuous Zero-Order Exposure to Xenobiotics (Intravenous Infusion) Introduction Compartmental Analysis References PK/TK Analysis of Xenobiotics Absorbed via an Extravascular Route of Administration (Oral Administration) Introduction Compartmental Analysis References PK/TK of Xenobiotics Absorbed through the Skin (Transdermal Absorption) Introduction Factors Influencing the Transdermal Absorption of Xenobiotics Mathematical Model for Prediction of Skin Concentration PK/TK of Percutaneous Absorption References PK/TK Analysis of Multiple Dosing Introduction Kinetics of Multiple Intravenous Bolus Injections--One-Compartment Model Kinetics of Multiple Oral Administration Effect of Changing Dose, Dosing Interval, and Half-Life on Accumulation in the Body and Fluctuation of Plasma Concentration Effect of Irregular Dosing Interval on the Plasma Concentration of Multiple-Dosing Regimen Multiple Dosing Kinetics--Two-Compartment Model Multiple Intravenous Infusions References Bioavailability, Bioequivalence, and Biosimilar Evaluations Introduction Peak Exposure, Total Exposure, and Early Exposure Bioavailability and First-Pass Metabolism Confirmation of Linearity of Relative and Absolute Bioavailability during Multiple Dosing Regimen Bioequivalence Study Biosimilars (Biosimilarity and Interchangeability) References Preclinical PK/TK and Clinical Trials Introduction Preclinical PK/TK PK/TK and Clinical Trials Dose and Dosing Regimen Adjustment for Patients with Variable Renal Impairments in Clinical Trials References Population Pharmacokinetics/Toxicokinetics Introduction Fixed Effect and Random Effect Parameters Linear and Nonlinear Mixed-Effects Models PLME Model Naïve-Pooled Data Approach (NPD) Two-Stage Approach Bayesian Approach Tools of Computational Statistics for PPK References Quantitative Extrapolation Interspecies Scaling/Low Dose Extrapolation Introduction Interspecies Scaling in Mammals Toxicogenomics Low Dose Extrapolation References Appendix A: Relevant Mathematical Concepts.