exam 4 Flashcards by P H

in many cases, they disposition of therapeutic monoconal antibody drugs in non-linear due to target-mediated elimination. For a monoclonal antibody demonstrating this behavior, saturation of the target-mediated pathway would be expected to

lead to a decrease in CL of the monoclonal antibody

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adminstration of high doses of IgG, as in IV IG therapy, may be expected to

increase the clearance of therapeutic IgG monoclonal antibodies

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general expectations for antibody pk include

good absorption following sq dosing
good absorption following IM dosing
bi-exponential disposition

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what is INCORRECT regarding anti-adalimumab abx (AAA)

-AAA develop in ~80% of pts receiving long-term therapy - AAA are likely to increase the clearance of ALL therapeutic monoclonal antibodies

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the major organ producing EOP is

kidneys

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F of rHuEOP following subq admins

increases with dose

IV= decreases

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clinical markers for EPO efficiency

hematocrit
RBC count
hemoglobin concentration

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some facts about warfarin

S-warfarin is primarily metabolized by CYP2c9
warfarin is highly protein bound, up to 99% mostly by albumin
warfarin is rapidly & well absorbed in the GI tract
R-warfarin exhibits a longer half-life than S-warfarin
anticoagulation is not achieved until 4-5 days after initiation of warfarin

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what is TMDD not a concern for the clinical dosing and monitoring of warfarin therapy?

-kinetics are nonlinear on first-dose but becomes dose-proportional on multiple dosing

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factors that can affect the anticoagulant effects & dosing of warfarin

co-admin with fluconazole
genetic variation in the CYP2c9 gene
genetic variation in the VCORC1 gene
co-admin with rifampin
warfarin cl decreasing with age

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new England journal things (2)

only one of the studies showed a statical difference supporting genotype-based warfarin dosing
these trails addressed the initiation of warfarin therapy and not maintenance dosing

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requirements for bayesian therapy

a prior population pk/pd model
feedback measurements of INR
computer software featuring a bayesian algorithm
the prescribed regimen and pt characteristics

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figure with distribution pattern of S/R warfarin

-S-warfarin cl follows a bimodal log-normal distribution pattern

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figure with pk of anti-human CD3 antibody in a pt at different occasions (1-10th day dosing lines)

the antibody pk demonstrates notable inter-occasion variability
the antibody pk demonstrates notable within-subject variability

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kaplan-meier plot for overall survival of pts with primary CNS lymphoma

pts with higher AUC values have longer survival time
less than 25% of pts with lower AUC values survived following 5 years of MTX tx
AUC vlue is a strong indicator for the efficiacy of MTX
measurements of AUC value is a good therapeutic practice for the treatment of primary CNS lymphoma ptts with MTX

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which of the following is a routinely used method for a priori determination of the dosage for chemotherapeutic drugs

dose determination based on renal or liver function
dose determination based on pts propensity for toxicity
dose determination based on pts pharmacogenetics
dose determination based on BSA or BW

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q LSM can still be used if it is not prospectively validated using the same

cancer indication

- brand names

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what controls the terminal half-life of EPO following subq admin

absorption from the subq site

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the major factor contributing to the clinical efficacy of EPO is

clearance

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what is NOT required for bayesian adaptive control of individual pt warfarin regimens?

feedback measurements of warfarin plasma concentrations

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what is correct about anti-digoxin immune fab

ADF is an example of an antibody that is used for immunotoxicotherapy
ADF is NOT protected bt FcRn, the fc-receptor of the neonate
ADF is in the same category of antibody application as infliximab & bevacizumab

response regarding anti-adalimumab antibodies (AAA)

in general, pts who develop high titiers of AAA demonstrate low exposures to adalimumab

figure with platimun AUC

-paclitaxel leads to a PD DDI with carboplatin that leads to decreased toxicity of carboplatin

what is the most common distribution pattern observed for the pk parameters while characterizing their inter-individual variability?

log-normal

what is the limit of BSA value that one could use to a priori calculate the dose of an anticancer agents for obese pts

2.2 m^2

which of the therapies is given prior to the surgical procedure to shrink tumor burden

neoadjuvant therapy

what is NOT a routinly used method for a priori determination of the dosage for chemotherapeutic drugs

dose determination based on pts tumor size and tumor growth rate

based on the duration-free survival vs time graph provided for methotrexate, which of the following PK matrix best correlates with the efficacy of MTX

Cmax

graph with unbound concentration of warfarin associated with similiar degree of anticoagulation response in a group of 97 pts

pharmacodynamic variability

inter-individual variability in the PD of a drug stems from

- genetic mutation in the receptors affected by the drug - environmental factors - concurrent drugs and diseases

2018 nobel prizes in med was awarded for

immunotherapy

inter-individual variability in the PD of a drug stems from

- genetic mutations in the receptors affected by the drug - environmental factors - concurrent drugs and diseases

the 2018 nobel prizes in medicine was awarded for which type of cancer tx

immunotherapy

general expectations for antibody pk includes

- good absorption following subq dosing - good absorption following intra-muscular dosing - bi-exponential disposition - small volume of distribution (3-9L)

Fc-receptor of the neonate fact things

- FcRn is also known as the brambell receptor | - FcRn protects IgG antibodies from intracellular catabolism

select the most appropriate response regarding protein pk

anti-drug antibodies typically lead to an increase in the rate of elimination of the therapeutic protein (drug)

select the most appropriate response regarding anti-adalimumuab antibodies (AAA)

- AAA develops in over 20% of pts recieving long-term therapy with adalimumab - pts who develop high titers of AAA demonstrate low concentration of adalimumab - pts who develop AAA are more likely to discontinue adalimumuab therapy due to tx failure

drug-drug interactions involving antibody drugs include:

- the effects of high-dose IgG therapy on monoclonal antibody clearance - the effects of immunosuppressive therapy on the development of ADA and on monoclonal antibody cl - the effects of bevacizumab on monoclonal antibody distribution to solid tumors

which of the following clearance mechanisms does contribute to nonlinear erythropoietin pk

receptor mediated endocytosis

which is the most relevant clinical marker for EPO efficacy

hemoglobin level

if the same dose of EPO is administered repeatedly to a pt, then the hemoglobin response:

is higher for sc injection than fir IV injections

adminstration of high doses of IgG may be expected to:

- increase the clearance of therapeutic IgG monoclonal antibodies - increase the clearance of endogenous IgG antibodies

four mechanistic categories of therapeutic application were presented for monoclonal antibody drugs,

- drug delivery - elimination of cells - alteration of cell function - immunotoxiciotherapy

more Fcr receptor of the neonates facts

- FcRn may become saturated in the presence of high concentrations of IgG - FcRn protects albumin from intracellular catabolism - FcRn demonstrates little to no affinity for IgG at pH 7.4

warfarin exhibits target-mediated drug disposition meaning:

drug binding to the target influences its pharmacokinetics

what is true regarding target-mediated drug disposition of small molecule drugs?

- the first dose shows linear kinetics | - the distribution phase for low doses is steep as compared to high doses

inter-ndividual variability in the PD of a drug stems from

- genetic mutation in the receptors affected by the drug - environmental factors - concurrent drugs and diseases

for anticancer agents which of the following PK matrix has been used to establish a correlation with efficacy/toxicity?

- AUC - Css - Cmax - time above a threshold concentrations

for which drugs is the leucovorin rescue therapy used?

methotrexate

a LMS can only be applied it it has been prospectively validated using the same:

- anticancer agent - dose - administration schedule - duration of infusion