Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Pharmacogenomics wikipedia , lookup
Drug interaction wikipedia , lookup
Discovery and development of cyclooxygenase 2 inhibitors wikipedia , lookup
Adherence (medicine) wikipedia , lookup
Tablet (pharmacy) wikipedia , lookup
Dydrogesterone wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Theralizumab wikipedia , lookup
Multiple dosing: Extravascular Administration Dr Mohammad Issa Saleh Multiple dosing: Extravascular Administration Multiple dosing: Extravascular Administration Concentration after n doses: KaFXo (1 e nK )e Kt (1 e nKa )e Kat Cn K Ka Vd ( Ka K ) 1 e 1 e Concentration at steady state Kt Kat e KaFXo e Css K Ka Vd ( Ka K ) 1 e 1 e n: number of doses, T: dosing interval Multiple dosing: Extravascular Administration Time to get to maximum conc after n doses: Ka(1 e nKa ) 1 e K 2.303 (tp)n log * nK Ka Ka K ) 1 e K (1 e Time to get to maximum conc at steady state: K Ka(1 e ) 2.303 (tp) ss log Ka Ka K ) K (1 e Accumulation ratio Accumulation can be determined by comparing the minimum plasma concentrations of drug at steady state and following the first dose: min CSS R min C N 1 e K FXo e Ka K Vd ( Ka K ) (1 e ) (1 e Ka ) FXo e K e Ka Vd ( Ka K ) 1 R (1 e K )(1 e Ka ) Accumulation ratio If the dose was administered in the elimination phase (no significant absorption occurs, accumulation ratio can be simplified into: 1 R K 1 e Time to reach steady state conc. Fraction of steady state conc obtained after the nth dose is given by: K e nKa Ka e nK fss 1 Ka K Ka K At very large values of Ka (i.e. Ka/K≥10), time to get to steady state can be represented as: n 1.44 t 0.5 ln( 1 fss) The AUC during a dosing interval at steady state is equal to the total AUC following a single dose (For linear PK) Average steady state conc The ‘‘average’’ plasma concentration of a drug at steady state for extravascularly administered dose can be calculated from: C average SS C 0 SS .dt FXo 1.44t0.5 FXo * KVd Vd Example 1 QJ is a 67-year-old, 80-kg male being treated for chronic obstructive pulmonary disease. Sustained-release oral theophylline is being added to his drug regimen. Assuming F = 1.0, V = 40 L, and t1/2 = 5 hours, compute an oral theophylline dose to be administered every 12 hours that would achieve a Css = 8 mg/L using the average steady-state concentration equation Xo C ss Vd 8 mg/L * 40 L *12 hr 533.3 mg 1.44t0.5 F 1.44 * 5 hr *1 av Example 2 A patient is taking 1000 mg sulfamethoxazole tablet every 12 hours for the treatment of urinary tract infection. Sulfamethoxazole is rapidly and completely absorbed after oral administration. What is the amount of sulfamethoxazole eliminated during one dosing interval at steady state ? Solution: amount eliminated during one dosing interval at steady state = amount administered during one dosing interval at steady state = maintenance dose= 1000 mg Example 3 During repeated administration of 60 mg indomethacin tablet every 12 hours (F=1) for the treatment of rheumatoid arthritis the AUC during one dosing interval was 8 mg-hr/L. What is the average indomethacin steady state plasma concentration during this dosing regimen (60 mg every 12 hours) ? C ss av AUC0 (at steady state) 8 mg.hr/L 0.67 mg/L 12 hr Example 4 JB is a 78-year-old, 100-kg male being treated with digoxin for heart failure. While receiving digoxin tablets 125 μg daily, an average steadystate digoxin concentration equal to 0.6 μg/L is obtained. Assuming F = 0.7, Compute digoxin clearance for the patient using the average steady-state concentration equation. Compute a new digoxin tablet dose for the patient that will achieve Css = 1.2 μg/L.. Example 4 1.Calculate clearance (Cl): At steady state: input rate = output rate dosing rate = elimination rate FX 0 average CSS * Cl FX 0 0.7 *125 g Cl 6.1 L/hr average * CSS 24 hr * 0.6 g/L Example 4 2- Calculate a new dose patient that will achieve Css = 1.2 μg/L: 0.6 µg/L 125 µg 1.2 µg /L ?? µg 1.2 Dose *125 250 g 0.6