Pharmacokinetics Flashcards
Mass spectrometry
Gold standard of chromatography
Narrow therapeutic drugs
CD FLP ST VW
PK info
Prescribing information
Clinical pharmacology of package insert
Goal of TDM
Better relationship between Cp and response than dose and response
Goal: optimize patients clinical outcomes by managing their medication regimen with measured drug concentrations
Pharmacodynamic markers
BP, cholesterol, coagulation time
High performance liquid chromatography
Lipophilic, stationary, long retention time
Hydrophilic, mobile, short retention time
Robustness
Rapid turnaround time
Specificity
Lack cross reactivity
Sensitivity
Detection of units nanograms
Concentration interpretation
Interpret after considering
Clinical response
Demographic and clinical status
Dosage regimen
PK characteristics of the drug
Transplant
Eye, blood easy
Lung difficult
Isograft
Genetically identical
Autograft
Same individual
Allograft
Same species
Cyclosporine ADME
Variable oral bioavailability
Highly bound to plasma lipoproteins
3A4 metabolism
Bile elimination
Monitor trough concentration for dose individualization
AE nephrotoxicity
No clear relationship between concentration and the risk of rejection
Tacrolimus
Incomplete and variable absorption
Food decreases absorption
Highly bound
Bile elimination
3A4 and 3A5 metabolism
AE: nephrotoxicity, neurotoxicity
Increased with PPI
3A5 metabolism
African American have more functional 3A5 and can metabolize tacrolimus better
Mycophenolic acid
MMF prodrug, teratogen
Sirolimus
mTOR inhibitor
Linear dose PK proportionality
3A4 metabolism, pgp efflux
Long half life, needs loading dose
3A4 inhibitors increase concentration
Erythro macrolides
CCB diltiazem verapamil
Azole antifungal
Grapefruit juice
3A4 inducers decrease concentration
Anticonvulsant pheny, pheno, carbamazepine
Glucocorticoids, rifampin, SJW
Theophylline
Antiinflammatory, steroid sparing
Half life shorter in children (higher clearance) higher Vd
Activates HDAC gene repression
Absorption is variable, not influenced by food
Binds to albumin
1A2 metabolism
Smoking increases clearance
Kidney metabolism
Water soluble molecules
GFR iohexol iothalamate gold standard
MDRD for staging CKD
Renal adjustment for drugs that are 30% renally eliminated
Renal dysfunction decreases 3A4
Liver metabolism
Metabolize lipophilic to more water soluble forms then renally eliminated
Child Pugh liver severity ABC
Hepatic encephalopathy
Ascites, albumin
Bilirubin, INR
Bile elimination
Non water soluble molecules
LogP
Positive lipophilic
Negative hydrophilic
Hemodialysis
Removes molecules <500D
Water soluble
Low Vd, unbound drugs
Continuous renal replacement
Up to 5000D
Can’t remove large Vd drugs
Sieving coefficient closer to 1 has better passage across filter
Immunoassay
Enzyme linked
