RT Book, Section
A1 Bauer, Larry A.
A2 DiPiro, Joseph T.
A2 Talbert, Robert L.
A2 Yee, Gary C.
A2 Matzke, Gary R.
A2 Wells, Barbara G.
A2 Posey, L. Michael
SR Print(0)
ID 1145217511
T1 Clinical Pharmacokinetics and Pharmacodynamics
T2 Pharmacotherapy: A Pathophysiologic Approach, 10e
YR 2017
FD 2017
PB McGraw-Hill Education
PP New York, NY
SN 9781259587481
LK accesspharmacy.mhmedical.com/content.aspx?aid=1145217511
RD 2024/04/16
AB KEY  CONCEPTS  Clinical  pharmacokinetics  is  the  discipline  that  describes  the  absorption,  distribution,  metabolism,  and  elimination  of  drugs  in  patients  requiring  drug  therapy.  Clearance  is  the  most  important  pharmacokinetic  parameter  because  it  determines  the  steady-state  concentration  for  a  given  dosage  rate.  Physiologically,  clearance  is  determined  by  blood  flow  to  the  organ  that  metabolizes  or  eliminates  the  drug  and  the  efficiency  of  the  organ  in  extracting  the  drug  from  the  bloodstream.  The  volume  of  distribution  is  a  proportionality  constant  that  relates  the  amount  of  drug  in  the  body  to  the  serum  concentration.  The  volume  of  distribution  is  used  to  calculate  the  loading  dose  of  a  drug  that  will  immediately  achieve  a  desired  steady-state  concentration.  The  value  of  the  volume  of  distribution  is  determined  by  the  physiologic  volume  of  blood  and  tissues  and  how  the  drug  binds  in  blood  and  tissues.  Half-life  is  the  time  required  for  serum  concentrations  to  decrease  by  one-half  after  absorption  and  distribution  are  complete.  It  is  important  because  it  determines  the  time  required  to  reach  steady  state  and  the  dosage  interval.  Half-life  is  a  dependent  kinetic  variable  because  its  value  depends  on  the  values  of  clearance  and  volume  of  distribution.  The  fraction  of  drug  absorbed  into  the  systemic  circulation  after  extravascular  administration  is  defined  as  its  bioavailability.  Most  drugs  follow  linear  pharmacokinetics,  whereby  steady-state  serum  drug  concentrations  change  proportionally  with  long-term  daily  dosing.  Some  drugs  do  not  follow  the  rules  of  linear  pharmacokinetics.  Instead  of  steady-state  drug  concentration  changing  proportionally  with  the  dose,  serum  concentration  changes  more  or  less  than  expected.  These  drugs  follow  nonlinear  pharmacokinetics.  Pharmacokinetic  models  are  useful  to  describe  data  sets,  to  predict  serum  concentrations  after  several  doses  or  different  routes  of  administration,  and  to  calculate  pharmacokinetic  constants  such  as  clearance,  volume  of  distribution,  and  half-life.  The  simplest  case  uses  a  single  compartment  to  represent  the  entire  body.  Factors  to  be  taken  into  consideration  when  deciding  on  the  best  drug  dose  for  a  patient  include  age,  gender,  weight,  ethnic  background,  other  concurrent  disease  states,  and  other  drug  therapy.  Cytochrome  P450  is  a  generic  name  for  the  group  of  enzymes  that  are  responsible  for  most  drug  metabolism  oxidation  reactions.  Several  P450  isozymes  have  been  identified,  including  CYP1A2,  CYP2C9,  CYP2C19,  CYP2D6,  CYP2E1,  and  CYP3A4.  Membrane  transporters  are  protein  molecules  concerned  with  the  active  transport  of  drugs  across  cell  membranes.  The  importance  of  transport  proteins  in  drug  bioavailability,  elimination,  and  distribution  is  continuing  to  evolve.  A  principal  transport  protein  involved  in  the  movement  of  drugs  across  biologic  membranes  is  P-glycoprotein.  P-glycoprotein  is  present  in  many  organs,  including  the  gastrointestinal  (GI)  tract,  liver,  and  kidney.  Other  transport  protein  families  include  the  organic  cation  transporters,  the  organic  anion  transporters,  and  the  organic  anion  transporting  polypeptides.  When  deciding  on  initial  doses  for  drugs  that  are  renally  eliminated,  the  patient’s  renal  function  should  be  assessed.  A  common,  useful  way  to  do  this  is  to  measure  the  patient’s  serum  creatinine  concentration  and  convert  this  value  into  an  estimated  creatinine  clearance  (CLcr  est).  For  drugs  that  are  eliminated  primarily  by  the  kidney  (more  than  or  equal  ...