Elective-session topics and objectives
Lecture A1 – Pharmacokinetics and Pharmacodynamics Modeling - James Uchizono
- The relationship among drug dose, pharmacokinetics (PK), and pharmacodynamics (PD).
- Types of Dose/PD relationships: linear vs non-linear.
- Drug-receptor interaction, and transduction to observed PD.
- Steady-state vs. non-steady-state experiments: the influence of PK on PD.
- Distributional effects: effect-compartment model.
- Effects of drug on endogenous substances: indirect-action models.
- How to differentiate between alternative mechanisms of drug action directly from the PK/PD observations and by means of mathematical modeling.
Lecture A2 - Macromolecule Pharmacokinetics - Sara Kenkare-Mitra
Learn about and understand:
- The current state of monoclonal antibodies as therapeutics.
- The basics of structure of monoclonal antibodies and those structural attributes critical in understanding their PK.
- Key differences between the PK of large and small molecules.
- What drives PK of monoclonal antibodies, in particular the role of receptor binding.
- Target-specific and non-specific binding of mAbs, and their respective roles in the clearance and distribution of antibodies.
- The definition of linearity/non-linearity of PK in the context of antibody therapeutics.
- Immunogenicity to antibody therapies and its impact on PK.
Lecture B1 – Nonlinear Pharmacokinetics - Deanna Kroetz
- List at least 10 sources of nonlinearities in drug absorption, distribution, and elimination.
- Apply the principle of superposition for the detection of nonlinear pharmacokinetics.
- Analyze pharmacokinetic data to determine which parameters, if any, are affected by concentration- or time-dependent mechanisms.
- Propose possible mechanisms for such dose- or time-dependent changes in pharmacokinetic parameters.
- Predict whether a drug will exhibit saturable metabolism given estimates of the Michaelis-Menten parameters, Vmax and KM, and knowledge of the therapeutic concentration range.
- Predict the relative importance of a capacity-limited metabolic pathway for a drug which is eliminated by parallel saturable and linear routes.
- Distinguish between saturable first-pass metabolism and capacity-limited systemic elimination.
- Estimate an individual’s Vmax and KM from steady-state blood levels for a drug eliminated almost entirely through a saturable metabolic pathway.
Lecture B2 - Pharmacogenomics in the Management of Variability - Kathleen Giacomini
- List three reasons why drug response may be variable among individuals.
- Define the terms: pharmacogenetics, polymorphism, phenotype, allele, homozygous, heterozygous, haplotype, nonsynonomous and synonomous coding, non-coding, intronic polymorphisms.
- Describe how reduced function genetic variants in the enzyme, thiopurine methyltransferase (TPMT), result in increased toxicity of the drug, 6-mercaptopurine.
- Describe how reduced function genetic variants in the enzyme, CYP2D6, may result in non-response to tamoxifen.
- Describe how a drug-drug interaction between two drugs that are ligands of CYP2D6 may phenocopy a reduced function genetic variant in CYP2D6.
- Draw a schematic of the conversion of irinotecan to SN-38 and include the elimination of SN-38 through glucuronidation. Indicate UGT1A1 in the schematic.
- List the common reduced function alleles of SLCO1B1 and their frequency in European, African and East Asian populations.