Pharmacokinetics

1-Zero Order: conc. Changes at a constant rate dc/dt = -Ko

C = -Ko T + Co

2-First order reaction: conc. Changes with respect to the remaining conc.Log C = log Co- K t / 2.31. T = 0.693/K (Imp.)2. Cl = K el x Vd (Imp.)3. Cl = 0.693Vd / T

4. The rate of elimination is the clearance times the concentration in the plasma

R oe = Cl x Cp5. Fraction of the total drug removed per unit time = Cl/Vd.

Half Life is constant

Compartments

One compartment1- IV Bolus

A-Drug Elimination is first Order Kel = Ke (Renal Execrition rate constant ) + Km (Metabolism rate constant )

B- Apparent volume of Distribution Vd :

Vd increase when drug distribute extravascularly.

2-Single Oral Dose:

Elimination + Absorption = First Order

AUC is determined using trapezoidal ruleLag time: at beginning of systemic dg absorption due to factors as stomach emptying

3-IV InfusionZero Order Absorption and First Order Elimination

Some oral controlled release drugs release by zero-order kinetics and have zero-order systemic absorption

R = Zero-Order rate of Infusion

Steady State Conc.

Css = R / Vd K

= R / CLt

First rate Order of Elimination

R = Css Vd K = Css CLtLoading Dose: given at the time of Infusion to produce Css without it it will take 3.32 T to reach 90% Css / 4.32 T 95% / 6.65 t 100 % .

Dl = Css Vd (Imp.) = R / K

This is important to keep the drug with narrow therapeutic index between MTC (minimum Toxic Conc. ) and MEC ( Minimum effective conc.)

4-Intermittent IV infusions

Used to prevent Cumulative Toxicity Ex. Gentamicin

5. Multiple Doses

Dose is given before the previous was eliminated leading to accumulation and steady state and the drug fluctuates between and Superposition principle: assumes that previous dose has no effect on the subsequent

Dosing Rate = Do (Size Of Dose) / T (Frequency of Dosing or Interval)Dosing Rate = clearance x desired plasma concentration

If Dosing rate is the same the average Drug Conc at steady state is the same.Ex 600 mg dose, 12 Hr Interval Dose Rate = 600/12 = 50

300 mg dose, 6 hr interval dose Rate = 300/6 = 50

However the Cmax and Cmin are different

Cmax in the higher doses with longer periods is higher and Cmin is lower compared to smaller doses over shorter periodsMultiple rapid IV Bolus

Oral Immediate Rlease Forms (Solution, Tablets , Caps )Given multiple times , rapid abosrbtion and slow elimination

Loading Dose Dl for multiple oral doses

If Dm is given at Dose interval = Elimination half life then Dl = 2 x MaintenanceMulticompartment wasnt done