Dosing Basics - How to

Determine the Right Amount

of Drug for a Patient
How can we determine the safest and most
effective dose of drug for a specific patient
• Determine a loading dose to start therapy
How can we determine the safest and most
effective dose of drug for a specific patient
• Determine a loading dose to start therapy
• Calculate the rate of infusion to achieve a desired Css and predict
Css from a given infusion
How can we determine the safest and most
effective dose of drug for a specific patient
• Determine a loading dose to start therapy
• Calculate the rate of infusion to achieve a desired Css and predict
Css from a given infusion
• Calculate a dosing regimen to achieve a desired Cav,ss, Cmax,ss or
Cmin,ss
How can we determine the safest and most
effective dose of drug for a specific patient
• Determine a loading dose to start therapy
• Calculate the rate of infusion to achieve a desired Css and predict
Css from a given infusion
• Calculate a dosing regimen to achieve a desired Cav,ss, Cmax,ss or
Cmin,ss
• Identify how serum concentrations accumulate during an infusion
or a multiple dosing regimen (and the role of 1 – e-kt)
How can we determine the safest and most
effective dose of drug for a specific patient
• Determine a loading dose to start therapy
• Calculate the rate of infusion to achieve a desired Css and predict
Css from a given infusion
• Calculate a dosing regimen to achieve a desired Cav,ss, Cmax,ss or
Cmin,ss
• Identify how serum concentrations accumulate during an infusion
or a multiple dosing regimen (and the role of 1 – e-kt)
• Adjust dosing regimens based on first-order linearity
The 3 Major Types of Dosing
The 3 Major Types of Dosing
• Loading Dose (single dose to achieve a desired C0)
The 3 Major Types of Dosing
• Loading Dose (single dose to achieve a desired C0)

• Continuous infusion (to achieve a desired Css)

The 3 Major Types of Dosing
• Loading Dose (single dose to achieve a desired C0)

• Continuous infusion (to achieve a desired Css)

• Intermittent Dosing
The 3 Major Types of Dosing
• Loading Dose (single dose to achieve a desired C0)

• Continuous infusion (to achieve a desired Css)

• Intermittent Dosing
(multiple doses to achieve a desired Cav,ss)
(multiple doses to achieve a desired Cmax,ss & Cmin,ss)
The 3 Major Types of Dosing
• Loading Dose (single dose to achieve a desired C0)

• Continuous infusion (to achieve a desired Css)

• Intermittent Dosing
(multiple doses to achieve a desired Cav,ss)
(multiple doses to achieve a desired Cmax,ss & Cmin,ss)
Serum Concentrations from a
Continuous Infusion

Rinf
100
(mg/hr)
CL (L/hr) 4
k (hr-1) 0.20
V (L) 20
Css (mg/L) 25.0
Serum Concentrations from a
Continuous Infusion
Rinf Rinf
Css = =
k × V CL
Rinf
100
(mg/hr)
CL (L/hr) 4
k (hr-1) 0.20
V (L) 20
Css (mg/L) 25.0
The Concept of % Lost as an
“Accumulation Factor”

If k = 0.2/h and t = 4 h, then e-kt = 0.45,

so 45% of the drug remains after 4 hours and 55% is
lost
The Concept of % Lost as an
“Accumulation Factor”
− Kt
e % remaining

If k = 0.2/h and t = 4 h, then e-kt = 0.45,

so 45% of the drug remains after 4 hours and 55% is
lost
The Concept of % Lost as an
“Accumulation Factor”
− Kt
e − Kt % remaining 1− e % lost

If k = 0.2/h and t = 4 h, then e-kt = 0.45,

so 45% of the drug remains after 4 hours and 55% is
lost
The Concept of % Lost as an
“Accumulation Factor”
− Kt
e − Kt % remaining 1− e % lost

If k = 0.2/h and t = 4 h, then e-kt = 0.45,

so 45% of the drug remains after 4 hours and 55% is
lost
1 – e-ktinf (% lost) defines the accumulation
to steady state during a continuous infusion
Determining Cinf from an Infusion

Rinf (mg/hr) 100

tinf (hr) 20
CL (L/hr) 4
V (L) 20
Css (mg/L) 25.0
k (hr-1) 0.20
Determining Cinf from an Infusion
R 𝑖𝑖𝑖𝑖𝑖𝑖
At steady-state…… 𝐶𝐶𝑠𝑠𝑠𝑠 =
𝐶𝐶𝐶𝐶

Rinf (mg/hr) 100

tinf (hr) 20
CL (L/hr) 4
V (L) 20
Css (mg/L) 25.0
k (hr-1) 0.20
Determining Cinf from an Infusion
R 𝑖𝑖𝑖𝑖𝑖𝑖
At steady-state…… 𝐶𝐶𝑠𝑠𝑠𝑠 =
𝐶𝐶𝐶𝐶
BEFORE steady-state : Drug accumulates to Css at a rate equal to : (1 − e − kt )

𝑅𝑅𝑖𝑖𝑖𝑖𝑖𝑖 × 1 − 𝑒𝑒 −𝑘𝑘𝑘𝑘𝑖𝑖𝑖𝑖𝑖𝑖
𝐶𝐶𝑖𝑖𝑖𝑖𝑖𝑖 =
𝐶𝐶𝐶𝐶
Rinf (mg/hr) 100
tinf (hr) 20
CL (L/hr) 4
V (L) 20
Css (mg/L) 25.0
k (hr-1) 0.20
Determining Cinf from an Infusion
R 𝑖𝑖𝑖𝑖𝑖𝑖
At steady-state…… 𝐶𝐶𝑠𝑠𝑠𝑠 =
𝐶𝐶𝐶𝐶
BEFORE steady-state : Drug accumulates to Css at a rate equal to : (1 − e − kt )

−𝑘𝑘𝑘𝑘𝑖𝑖𝑖𝑖𝑖𝑖 𝑅𝑅𝑖𝑖𝑖𝑖𝑖𝑖 × 1 − 𝑒𝑒 −𝑘𝑘𝑘𝑘𝑖𝑖𝑖𝑖𝑖𝑖

𝐶𝐶𝑖𝑖𝑖𝑖𝑖𝑖 = 𝐶𝐶𝑠𝑠𝑠𝑠 × 1 − 𝑒𝑒 𝐶𝐶𝑖𝑖𝑖𝑖𝑖𝑖 =
𝐶𝐶𝐶𝐶
Rinf (mg/hr) 100
tinf (hr) 20
CL (L/hr) 4
V (L) 20
Css (mg/L) 25.0
k (hr-1) 0.20
How Drug Dosing Relates to CL
V = 20 L CL = 4L/hr Css = 10 mg/L

4 L are cleared of drug per hr

20 L Tank
..... ..... ..... ..... .....
..... ..... ..... ..... .....
..... ..... .....
..... ..... CL = .....
.....
.....
.....
.....
4 L/hr .....
.....
..... ..... ..... ..... .....
..... ..... ..... ..... .....
How Drug Dosing Relates to CL
V = 20 L CL = 4L/hr Css = 10 mg/L

At SS:
4 L are cleared of drug per hr
Replace the drug in 4 L every hr
20 L Tank
..... ..... ..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... CL = .....
..... ..... ..... ..... ..... .....
.....
.....
.....
4 L/hr .....
.....
..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... ..... ..... .....
How Drug Dosing Relates to CL
V = 20 L CL = 4L/hr Css = 10 mg/L

At SS:
4 L are cleared of drug per hr
Replace the drug in 4 L every hr
20 L Tank
..... ..... ..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... CL = .....
..... ..... ..... ..... ..... .....
.....
.....
.....
4 L/hr .....
.....
..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... ..... ..... .....
..... ..... ..... ..... ..... ..... ..... ..... ..... .....

Dosing needs to be 40 mg/hr to keep the Css at 10 mg/L

Let’s Pause for Brain Exercise
If a patient receives a drug by continuous infusion
• The Cinf will be equal to the Css times e-ktinf
• Rinf is the fraction of Cinf as compared to Css
• The Css will be 20 mg/L if the Rinf is 100 mg/h and the CL is 5
L/h
• A and B are correct, but C is NOT
• A, B and C are all correct
Let’s Pause for Brain Exercise
If a patient receives a drug by continuous infusion
F • The Cinf will be equal to the Css times e-ktinf
• Rinf is the fraction of Cinf as compared to Css
• The Css will be 20 mg/L if the Rinf is 100 mg/h and the CL is 5
L/h
• A and B are correct, but C is NOT
• A, B and C are all correct
Let’s Pause for Brain Exercise
If a patient receives a drug by continuous infusion
F • The Cinf will be equal to the Css times e-ktinf
F • Rinf is the fraction of Cinf as compared to Css
• The Css will be 20 mg/L if the Rinf is 100 mg/h and the CL is 5
L/h
• A and B are correct, but C is NOT
• A, B and C are all correct
Let’s Pause for Brain Exercise
If a patient receives a drug by continuous infusion
F • The Cinf will be equal to the Css times e-ktinf
F • Rinf is the fraction of Cinf as compared to Css
T • The Css will be 20 mg/L if the Rinf is 100 mg/h and the CL is 5
L/h
• A and B are correct, but C is NOT
• A, B and C are all correct
Let’s Pause for Brain Exercise
If a patient receives a drug by continuous infusion
F • The Cinf will be equal to the Css times e-ktinf
F • Rinf is the fraction of Cinf as compared to Css
T • The Css will be 20 mg/L if the Rinf is 100 mg/h and the CL is 5
L/h
• A and B are correct, but C is NOT
• A, B and C are all correct
Applications of a Loading Dose
• Achieves therapeutic effect rapidly by filling the tank
Applications of a Loading Dose
• Achieves therapeutic effect rapidly by filling the tank
• Clearance has NO EFFECT on the size of loading dose
• Loading dose depends on V and desired C0
Applications of a Loading Dose
• Achieves therapeutic effect rapidly by filling the tank
• Clearance has NO EFFECT on the size of loading dose
• Loading dose depends on V and desired C0
• The 3 possible results of a loading dose
LD too high
Applications of a Loading Dose
• Achieves therapeutic effect rapidly by filling the tank
• Clearance has NO EFFECT on the size of loading dose
• Loading dose depends on V and desired C0
• The 3 possible results of a loading dose
LD too high LD too low
Applications of a Loading Dose
• Achieves therapeutic effect rapidly by filling the tank
• Clearance has NO EFFECT on the size of loading dose
• Loading dose depends on V and desired C0
• The 3 possible results of a loading dose
LD too high LD too low LD just right