NAPLEX / Pharmaceutics Kinetics

C = Dose/Vd
C= 1500mg/67.5L = 22.2 mg/L

400 mg IV Q8H = 1200 mg daily
Difference between IV and PO bioavailability = 100% - 70% = 30 % =0.03 (we will need 30% more of PO drug to receive the same daily dose of Ciprofloxacin)
1200mg x 0.30 = 360mg
360mg + 1200mg = 1560 mg or 500 mg TID

-T>MIC: the pharmacodynamics outcome that is correlated with efficacy for time dependent drugs; increased bacterial killing is based on the percentage of time the concentration exceeds the MIC. Drugs reach a saturable killing rate, therefore, increasing drug concentrations more will not affect the bacterial activity. Example of drugs: Penicillins, cephalosporings, monobactmas, clindamycin, macrolides, linezolid, tetracyclines.
-Peak/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. The rate and extend of killing of bacteria will increase with increased drug concentrations relative to the MIC. Administer higher doses with a decreased frequency of administration. Examples of drugs: aminoglycosides, floroquinolones, ketolide, metronidazole, oritavancin
-AUC/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. It measures the AUC relative to the MIC of the organisms. Administer higher doses with a decreased frequency of administration. Example of drugs: floroquinolones, macrolides, tetracyclines, vancomycin.

-T>MIC: the pharmacodynamics outcome that is correlated with efficacy for time dependent drugs; increased bacterial killing is based on the percentage of time the concentration exceeds the MIC. Drugs reach a saturable killing rate, therefore, increasing drug concentrations more will not affect the bacterial activity. Example of drugs: Penicillins, cephalosporings, monobactmas, clindamycin, macrolides, linezolid, tetracyclines.
-Peak/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. The rate and extend of killing of bacteria will increase with increased drug concentrations relative to the MIC. Administer higher doses with a decreased frequency of administration. Examples of drugs: aminoglycosides, floroquinolones, ketolide, metronidazole, oritavancin.
-AUC/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. It measures the AUC relative to the MIC of the organisms. Administer higher doses with a decreased frequency of administration. Example of drugs: floroquinolones, macrolides, tetracyclines, vancomycin.

F = (AUC PO)/(AUC IV) x (Dose IV)/(Dose PO)
F = 1/1 x 25/100 = 0.25 X 100% = 25%

-T>MIC: the pharmacodynamics outcome that is correlated with efficacy for time dependent drugs; increased bacterial killing is based on the percentage of time the concentration exceeds the MIC. Drugs reach a saturable killing rate, therefore, increasing drug concentrations more will not affect the bacterial activity. Example of drugs: Penicillins, cephalosporings, monobactmas, clindamycin, macrolides, linezolid, tetracyclines.
-Peak/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. The rate and extend of killing of bacteria will increase with increased drug concentrations relative to the MIC. Administer higher doses with a decreased frequency of administration. Examples of drugs: aminoglycosides, floroquinolones, ketolide, metronidazole, oritavancin.
-AUC/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. It measures the AUC relative to the MIC of the organisms. Administer higher doses with a decreased frequency of administration. Example of drugs: floroquinolones, macrolides, tetracyclines, tigecycline, vancomycin.

It takes 5 half lives for a drug to be theoretically completely eliminated (98% eliminated). 5 X 10 hours = 50 hours.

Cmax = Dose/Vd
Cmax = 1000mg/24.5L = 40.8 mg/L

Ke = 0.693/(t1/2 ) = 0.14 h-1
C = Cmax x e-ke x t = 40.8 x e-0.14 x 12 = 7.6 mg/L

C = Dose/Vd = 2000mg/18L
= 111 mg/L

k= 0.693/(t1/2 )= 0.345 Fraction remaining after 1 half life (2 hours) = e^(-kt)= e – 0.345 x 2= 0.50
Amount remaining after 1 half life (2 hours) = 0.50 x 111mg/mL = 55.5 mg/mL
Amount remaining after 2 half lives (4 hours) = 0.25 x 111 mg/mL = 27.75 mg/mL
Amount remaining after 3 half lives (6 hours) = 0.125 x 111 mg/mL = 13.875 mg/mL
Amount remaining after 4 half lives (8 hours) = 0.0625 x 111 mg/mL = 6.93 mg/mL
Since the MIC of Cefepime is 8, it will take 4 half lives for cefepime to reach a concentration of 6.93 mg/mL, which is a blood concentration below MIC.

It will take 4 half lives for cefepime to reach a concentration of 6.93 mg/mL Since the MIC of Cefepime is 8, it will take approximately 8 hours for cefepime to reach a concentration of 6.93 mg/mL, which is a blood concentration below MIC.

T>MIC = ln ( Dose/(Vd x MIC) ) x (t1/2)/ln⁡〖(2)〗 x 100/DI
T>MIC = ln ( (1000 mg)/(18 L x 8) ) x (2 hours)/ln⁡〖(2)〗 x 100/(12 hours)
T>MIC = 46.7%

T>MIC = ln ( Dose/(Vd x MIC) ) x (t1/2)/ln⁡〖(2)〗 x 100/DI
T>MIC = ln ( (2000 mg)/(18 L x 8) ) x (2 hours)/ln⁡〖(2)〗 x 100/(12 hours)
T>MIC = 63.3%

Oral vancomycin is not absorbed or metabolized, rather it is excreted in the feces unchanged, making it a drug of choice for the treatment of C. difficile infections. Serum concentrations with oral vancomycin should not be measured.

-T>MIC: the pharmacodynamics outcome that is correlated with efficacy for time dependent drugs; increased bacterial killing is based on the percentage of time the concentration exceeds the MIC. Drugs reach a saturable killing rate, therefore, increasing drug concentrations more will not affect the bacterial activity. Example of drugs: Penicillins, cephalosporings, monobactmas, clindamycin, macrolides, linezolid, tetracyclines.
-Peak/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. The rate and extend of killing of bacteria will increase with increased drug concentrations relative to the MIC. Administer higher doses with a decreased frequency of administration. Examples of drugs: aminoglycosides, floroquinolones, ketolide, metronidazole, oritavancin.
-AUC/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. It measures the AUC relative to the MIC of the organisms. Administer higher doses with a decreased frequency of administration. Example of drugs: floroquinolones, macrolides, tetracyclines, vancomycin.

t1/2 = (0.693 x Vd)/CL
t1/2 = (0.693 x 700mL/kg x67kg)/(120mL/min)
= 270 minutes = 4.5 h

Ke= ln⁡〖C1-ln⁡C2 〗/(t2-t1)
Ke= ln⁡〖(24.5)-ln⁡〖(14.5)〗 〗/(37-32) = 0.104
T1/2= 0.693/0.104 = 6.66 h = 7h

F = (AUC PO)/(AUC IV) x (Dose IV)/(Dose PO)
F = 1/1 x 50/100 = 0.5 X 100% = 50%

Ke= ln⁡〖C1-ln⁡C2 〗/(t2-t1)
Ke= ln⁡〖(6.5 mg/L)-ln⁡〖(1.2 mg/L)〗 〗/((14-9) ) = 0.34 h-1
T1/2= 0.693/0.34 = 2.1 h

Acidic drugs are primarily bind to albumin (highly protein bound). Drugs that are highly protein/plasma bound tend to stay in the blood longer, resulting in a lower volume of distribution. Drugs that primarily distribute into tissue have a high volume of distribution.

-T>MIC: the pharmacodynamics outcome that is correlated with efficacy for time dependent drugs; increased bacterial killing is based on the percentage of time the concentration exceeds the MIC. Drugs reach a saturable killing rate, therefore, increasing drug concentrations more will not affect the bacterial activity. Example of drugs: Penicillins, cephalosporings, monobactmas, clindamycin, macrolides, linezolid, tetracyclines.
-Peak/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. The rate and extend of killing of bacteria will increase with increased drug concentrations relative to the MIC. Administer higher doses with a decreased frequency of administration. Examples of drugs: aminoglycosides, floroquinolones, ketolide, metronidazole, oritavancin.
-AUC/MIC: the pharmacodynamics outcome that is correlated with efficacy for concentration depend drugs. It measures the AUC relative to the MIC of the organisms. Administer higher doses with a decreased frequency of administration. Example of drugs: floroquinolones, macrolides, tetracyclines, vancomycin.

Basic drugs are less protein bound and therefore readily distribute into tissue, resulting in a higher volume of distribution. These drugs often stay for longer periods of time in organs and tissues, often leading to higher concentrations, narrower therapeutic index and decreased clearance.

There is a drug interaction between levofloxacin and amiodarone, which may increase the risk of QT prolongation. Levofloxacin is associated with QT prolongation and rarely torsades de pointes. Amiodarone also has a risk of QT prolongation and torsades de pointes. This drug interaction is possible for days to weeks after amiodarone is discontinued because amiodarone has a long half-life. There is also a drug interaction with furosemide and amiodarone. Caution must be used because loop diuretics can lower potassium and magnesium levels, which can cause amiodarone to not work effectively, but patient is on electrolyte replacement protocol and on it for short duration. Reference: Gold Standard, Inc. Levofloxacin. Clinical Pharmacology [database online]. Available at: https://www.clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=746&sec=moninte&t=0. Accessed: May 18, 2016.
Gold Standard, Inc. Amiodarone. Clinical Pharmacology [database online]. Available at: https://www.clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=25&sec=moninte&t=0. Accessed: May 18, 2016.