Non-linear Pks

Question 1

What is the michaelis menten equation used to measure

Answer 1

enzyme kinetics or enzymatic reactions

Question 2

describe the michaelis menten equation and each parameter

Answer 2

• Rate of Reaction or V = VmaxC/Km + C where
• Vmax = maximum velocity of the reaction
  
  • fcn of total amount of enz available to take part in the rxn
• C = concentration of the reacting compound
• Km = Michaelis Menten constant
  
  • relates to affinity of the enzyme

Question 3

what can the Michaelis Menten equation be used to determine

Answer 3

the rate of metabolism of a drug involving enzymatic controlled rxns

Question 4

how is the Michaelis Menten equation re-written as it relates to enzyme controlled reactions of drugs

Answer 4

• Rate of metab = Vmax Cp/Km + Cp

Question 5

As it relates to metabolism define C and Km

Answer 5

C = Cp or plasma concentration

Km = Vmax/2 has concentration units e.g. g/L

Question 6

define clearance based upon the Michaelis menten equation

Answer 6

Cl = Vmax /Km

Question 7

Rate of Metab = Vmax is what order of equation

Answer 7

• zero order kinetic process
• rate of metabolism is independent of plasma concentration

Question 8

how is clearance calculated for nonlinear pk

Answer 8

Cl = Vmax/ Km + Cp

Question 9

as it relates to clearance (Cl = Vmax/ Km + Cp) when Cp increases Clearance increases or decreases

Answer 9

decreases, it is inversely proportional

Question 10

as it relates to Rin = ClCpss = Vmax Cpss/Km + Cpss what happens to Rin as it approaches Vmax

what is this equation

Answer 10

• Cpss increases exponentially with small changes in dosing rate
• therefore dose adjustment can be difficult
• dosgin equation

Question 11

what does the term capacity limited mean

Answer 11

• capacity limited elimination is the point where enzymes are working at Vmax and any further increase in drug concentration has no additional impact on drug metabolism

Question 12

what are the causes of non-linear elimination (4)

Answer 12

• capacity limited metabolism
• more rapid elimination due to reabsorption within kidney tubules
• increased rate of elimination due to enzyme induction
• change in clearance or apparent volume of distribution and half life due to staturable protien binding in plasma or tissues

Question 13

what are causes of non-linearity in absorption phase (2)

Answer 13

• decrease rate and extend of absorption due to
  
  • saturation of active absorption process or
  • limited solubility at high conc
• increased apparent absorption due to saturation of first pass metabolism at higher doses

Question 14

when a drug exhibits non linear (i.e. Michaelis Menten) elimination kinetics estimation of bioavailability is easy or difficult and why?

Answer 14

• difficult
• because AUC is not proportional to dose absorbed
• more of the dose escapes metabolism at higher doses b/c of saturation of the elimination pathway

Question 15

what are some examples of drugs that display non-linear pharmacokinetics (4)

Answer 15

• phenytoin
• aspirin
• diltiazem
• alcohol

Question 16

nonlinearity frequently occurs at low or high doses

Answer 16

high

Question 17

when does nonlinearity become problematic when establishing bioavailability

Answer 17

when a drug has a narrow therapeutic range