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# CHAPTER 2: First-Order Kinetics Page49 6) If the half-life for decomposition of a

Page 48. 2) Plot the following data on both semilog drug is 12 hours, how long will it take for 125mg of
graph paper and standard rectangular coordinates. the drug to decompose by 30%? Assume first-order
Time (min) Drug A (mg) kinetics and constant temp.
4 70 C0 = 125mg
10 58 C = 125mg X 0.70 = 87.5 mg
20 42 t 1/2 = 12 hours
30 31
60 12 k = 0.693 = 0.693
90 4.5 t1/2 12 hrs
120 1.7 k = 0.0578 hrs -1

## -k= 2.3 ( log C – log C0 ) t = 2.3 ( log C – log C0 )

Time -k
C0 = 70mg t0 = 4 mins. t = 2.3 ( log 87.5 – log 125 )
C = 42mg t = 20 mins 0.0578 hrs-1
t = 6.16 hours
-k = 2.3 ( log 42 – log 70 )
20mins – 4mins Page 49 5) How many half-lives (t1/2) would it take
-k = 2.3 (1.6232 – 1.8451) for 99.9% of any initial conc. of a drug to
16mins decompose?
-k = 0.0319 min-1 t1/2 = X
C0 = 100 mg X 0.999 = 99.9 mg
t1/2 = 0.693 = 0.693 C = 100 mg X 0.001 = 0.1 mg
k 0.0319
1
t /2 = 21.72 mins t = 2.3 ( log C – log C0 ) (t1/2)
-k
Page 49 4) A solution of a drug was freshly t = 2.3 ( log 0.1mg – log 99.9mg)
prepared at a concentration of 300 mg/mL. After 30 -0.693
days at 25o C, the drug conc. In the solution was 75 t = 9.96 (t1/2)
mg/mL.

## a) Assuming first order kinetics, when will the drug

decline to one-half of the original conc.?
C0 = 300 mg/mL
C = 75mg/mL
t = 30 days

## -k= 2.3 ( log C – log C0 )

Time
-k = 2.3 ( log 75mg/mL – log 300 mg/mL )
30 days
-k = 0.0462 days -1

## t1/2 = 0.693 = 0.693

k 0.0462
1
t /2 = 15 days
Quiz: 20mcg dissolved in an unknown vol. of H2O
1
Time (hr) Drug A (mcg/mL) PAGE 69 #1) A 70kg volunteer is given an
0.25 8.21 intravenous dose of an antibiotic, and serum drug
0.50 7.87 conc. were determined at 2 hours and 5 hours after
1.00 7.23 administration. The drug conc. were 1.2 and 0.3
3.00 5.15 mcg/mL, respectively. What is the biologic half-life
6.00 3.09 for this drug, assuming first-order kinetics?
12 1.11
18 0.40 Wt. of Px = 70kg Cp0 = 1,2 mcg/mL
a. Constant rate? t0 = 2 hours Cp = 0.3 mcg/mL
-k= 2.3 ( log C – log C0 ) t = 5 hours t1/2 = X
Time
-k= 2.3 ( log 7.23 – log 8.21 ) -k= 2.3 ( log Cp – log Cp0)
1-0.25 Time
-k= 0.1693 hours-1 -k= 2.3 ( log 0.3 – log 1.2)
5 hours – 2 hours
b. t1/2 ? -k = -0.4616 hours-1
t1/2 = 0.693 = 0.693
k 0.1693 t1/2 = 0.693 = 0.693
t 1/2 = 4.1 hours k 0.4616
1
t /2 = 1.50 hours
c. Concentration at time 0
log C0 = -kt + log C #3 A new drug was given in a single intravenous
2.3 dose of 200mg to an 80kg adult male Px. After
log C0 = (0.1693)(1) + log 7.23 6hrs. the plasma drug conc. of drug was
2.3 1.5mg/100mL of plasma. Assuming that the
apparent VD is 10% of body weight, compute the
C0 = 8.56 mcg/mL total amount of drug in the body fluids after 6 hrs.
What is the half-life of this drug?
d. Volume of Water Wt. of Px = 80kg Cp = 1.5 mg/100mL = 0.015
8.56 mcg = 20 mcg t = 6 hours Dose = 200 mg
1mL X VD = 10% of total BW = 10 X 0.1 = 8L; 8000mL
Cp0 = Dose = 200mg
X= 2.34 mL VD 8000mL
Cp0 = 0.025 mg/mL

## -k= 2.3 ( log Cp – log Cp0)

Time
-k= 2.3 ( log 0.015 – log 0.025)
6
-k= 0.085hours-1

## t1/2 = 0.693 = 0.693

k 0.085 hr
1
t /2 = 8.15 hours

## PAGE 69 #2) A 50kg woman was given a single IV

CHAPTER 3: dose of an antibacterial drug at a dose level of
6mg/kg. Blood samples were taken at various time
2
intervals. The conc. of the drug (Cp) was Cp = 2 mcg/mL
determined in the plasma fraction of each blood
sample and the ff. data were obtained: Time = 2.3 ( log Cp – log Cp0)
Time (hr) Drug A (mcg/mL) -K
0.25 8.21 Time = 2.3 ( log 2 – log 8.57)
0.50 7.87 -0.1693 hour-1
1.00 7.23 Time = 8.59 hours
3.00 5.15
6.00 3.09 c. How long would it take for 99.9% of this drug to
12.0 1.11 be eliminated?
18.0 0.40 t=x
a. What are the values for VD, k, & t 1/2 for this Cp0 = 8.57 mcg/mL
drug? Cp = 100%–99.9% = 0.00857
Wt. of Px = 50 kg Cp = 0.00857 mcg/mL
Usual dose = 6mg/kg Time = 2.3 ( log 0.00857 – log 8.57)
Dose = 6mg/kg x 50kg = 300mg -0.1693 hours
Cp0 = 8.21 mcg/mL Time = 40.76 hours
Cp = 7.23 mcg/mL
t0 = 0.25 hour d. If the dose of the antibiotic were doubled exactly,
t = 1 hour what would be the increase in duration of activity?
VD? k? t 1/2? t=x
Cp0 = 8.57 mcg/mL x 2
-k = 2.3 ( log 7.23 – log 8.21) Cp0 = 17.14 mcg/mL
1 – 0.25 Cp = 2 mcg/mL
-k = 0.1693 hours-1
Time = 2.3 ( log 2 – log 17.14)
t 1/2 = 0.693 = 0.693 -0.1693 hours
k 0.1693 Time = 12.67 hours
1
t /2 = 4.09 hours

## log Cp0 = -kt + log Cp

2.3
log Cp0 = (0.1693) (0.25) + log 8.21
2.3
log Cp0 = 0.9327
Cp0 = antilog 0.9327
Cp0 = 8.57mcg/mL

## VD = Dose = 300mg = 300,000 mcg

Cp0 8.57mcg/mL 8.57 mcg/mL
VD = 35,005 mL
VD = 35L
Page 70 #4) A new antibiotic drug was given in a
b. This antibacterial agent is not effective at a single intravenous bolus of 4mg/kg to 5 healthy
plasma conc. of less than 2mcg/mL. What is the male adults ranging in age from 23 to 38 years
duration of activity for this drug? (average weight 75kg). The pharmacokinetics of
t=x the plasma drug conc.-time curve for this drug fits a
Cp0 = 8.57 mcg/mL one-compartment model. The equation of the curve
3
that best fits the data is Cp=78e-0.46t Determine the DB = 47538.41 mcg x 1mg/1000mcg
ff.(assume units mcg/mL for Cp & hr for t) DB = 47.54mg
a. What is the t1/2?
Cp=78e-0.46t e. Predict what body water compartment this drug
Cp = Cp0e-0.46t might occupy & explain why you made this
Cp0 = 78mcg/mL prediction.
K = 0.46 hr-1 %BW = VD___ x 100
t1/2 = 0.693 = 0.693 Wt. of Px
k 0.46hr-1 VD = 3846.15mL = 3846.15g or 3.846kg
t1/2 = 1.5 hours VD = 3.846___ x 100
75kg
b. What is the VD? VD = 5%
Dose = 4mg/kg
Wt. of Px = 75kg f. Assuming the drug is no longer effective when
Dose = 4mg/kg x 75kg = 300mg levels decline to less than 2mcg/mL, when
= 300 mg x1000mcg should you administer the next dose?
1mg
= 300000 mcg Cp = 2 mcg/mL
VD = Dose = 300000 mcg Time = 2.3 ( log Cp – log Cp0)
Cp0 48mcg/mL -K
VD = 3,846.15 mL Time = 2.3 ( log 2 – log 78)
-0.46
c. What is the plasma level of the drug after 4 Time =7.96 hours
hours?
Cp0 = 78
Time = 4hours
log Cp = -kt + log Cp0
2.3

## log Cp = (-0.46)(4) + log 78

2.3
log Cp = 1.09
Cp = antilog 1.09
Cp = 12.36 mcg/mL

d. How much drug is left in the body after 4 hours? Page70 #6) A drug has an elimination t1/2 of 6 hrs.
DB = ? & follows first-order kinetics. If a single 200mg dose
VD = Dose is given to an adult male patient (68kg) by IV bolus
Cp injection, what percent of the dose is lost in 24 hrs?
DB = VD CP % Drug lost = C0 – C x 100
DB = (3846.15mL)(12.36mcg/mL) C0
t1/2 = 6hrs.
4
C0/Drug = 200mg DB = 12.36mg
T = 24 hrs.
c. The time for the drug to decline to 0.5mcg/mL,
k = 0.693 = 0.693 the minimum inhibitory of streptococci is
t1/2 6 95mcg/mL?
k = 0.1155 hr-1 C0 = 95mcg/mL
log C = -kt + log C0 C = 0.5mcg/mL
2.3 Time = 2.3 ( log C – log C0)
log C = (0.1155)(24) + log 200 -K
2.3 Time = 2.3 ( log 0.5 – log 95)
C = antilog 1.096 -0.924 hr-1
C = 12.47 mg Time = 5.67hrs

% Drug lost = 200 – 12.47 x 100 Page71 #9 If the amount of drug in the body
200 declines from 100% of the dose (IV Bolus injection)
% Drug lost = 93.77% to 25% of the dose in 8hours, what is the
elimination half-life for this drug? (1st order kinetics)
#8) A single IV bolus injection containing 500mg of CO = 100%
cefemandole nafate is given to an adult female C = 25%
patient (63yrs, 55 kg) for a septicemia infection. T = 8 hours
The apparent volume of distribution is 0.1L/kg & the
elimination half-life is 0.75hr. Assuming the drug is -k= 2.3 ( log C – log C0)
eliminated by first-order kinetics & may be Time
described by one-compartment model, calculate -k= 2.3 ( log 25 – log 100)
the ff. 8 hours
Dose = 500mg -k = 0.1730 hour-1
Wt. of Px = 55kg
VD = 0.1L/kg x 55kg = 5.5L x 1000mL/L = 5,500mL t1/2 = 0.693 = 0.693
t1/2 = 0.75 kg k 0.1730hr-1
1
t /2 = 4 hours
a. Cp0 = Dose = 500mg
VD 5,500mL
Cp0 = 0.09mg/mL

b. The amount of drug in the body 4hrs. after the Page71 #10) A drug has an elimination half-life of 8
dose is given. hours and follows 1st order elimination kinetics. If a
DB = -kt + log DB0 single dose 600mg dose is given to an adult patient
2.3 (62kg) by rapid inj. What percent of the dose is
Log DB = (0.924hrs-1)(4hrs) + log 500 eliminated in 24 hrs. assuming the apparent VD is
2.3 400mL/kg? What is expected plasma drug conc.
DB = 1.092 (antilog) (CP) at 24 hours postdose?
t1/2 = 8hours Wt. of Px = 62kg
5
Dose = 600 mg VD = 400mL/kg KO 0.77mg/min
1
T = 24 hours t /2 = 62.34 mins.

## K = 0.693 = 0.693 Page49 #7) Exactly 300 mg of a drug is dissolved

Time 8 hours into an unknown volume of distilled water. After
K = 0.0866 hour-1 complete dissolution of the drug, 1.0mL samples
Log DB = log drug + (-k)(time) were removed and assayed for the drug. The ff.
2.3 results were obtained.
Time (hr) Drug A (mg/mL)
Log DB = log 600 + (0.0866 hour-1)(24hours) 0.5 0.45
2.3 2.0 0.3
Log DB = 1.8745 Dose = 300mg VH2O = ?
DB = antilog 1.8745 CO = 0.45 mg/mL tO = 0.5 hour
DB = 74.90 mg C = 0.3 mg/mL t = 2 hours

## % Drug lost = C0 – C x 100 -kO = C – CO = 0.3mg/mL – 0.45mg/mL

C0 t - tO 2 hours – 0.5 hour
% Drug lost = 600mg – 74.90mg x 100 -kO = 0.1 mg/mL/hour
600mg
% Drug lost = 87.5% CO = C + KOt
= 0.45mg/mL + (0.1mg/mL/hr)(0.5hour)
CP = 74.90 mg____ = 74.90mg CO = 0.5mg/mL
0.4L/kg x 62 kg 24.8L
CP = 3.02 mg/L 0.5mg = 300mg
1mL x
ClCR = [140 – AGE] [body weight (kg)] X = 600mL
72 [CrSR]

ZERO-ORDER KINETICS
EX #1) Time (hr) Drug A (mg)
10 96
20 89
40 73
60 57
90 34
120 10
130 2.5

## 1. Plasma sample from a patient were collected

-kO = ? tO = 10mins. after a dose of 10mg of drug as ff.
CO = 96mg t = 40mins Time (hr) Concentration (mg/mL)
C = 73mg 0.25 5.43
0.50 2.85
-k = C – CO = 73mg – 96mg
t - tO 40mins – 10mins a. Assuming first order kinetics when will the drug
-k = 0.77 mg/min decline to ½ of the original concentration.
b. Assuming zero order kinetics.
t1/2 = 0.5 CO = 0.5 (96mg)
6
T0 = 0.25 C0 = 5.43
T = 0.50 C = 2.85 b. What is VD?
VD = Dose = 350,000 mcg
1. First-Order Kinetics Cp0 45 mcg/mL
-k = 2.3 ( log C – log C0) VD = 7,777.78 mL
Time
-k = 2.3 ( log 2.85 – log 5.43) c. What is the plasma level of the drug after
0.50-0.25 5hours?
-k = -2.5756 hour-1 Cp = 45 e -0.17(5hours)
Cp = 19.23 mcg/mL
t1/2 = 0.693 = 0.693
k 2.5756hr-1 d. How much drug left in the body after 5hrs?
t1/2 = 0.27 hour Dose = VD Cp0
Dose = (7,777.78 mL)(19.23 mcg/mL)
2. Zero-order kinetics Dose = 149,566.71 mcg
-k0 = C – CO = 2.85mg/mL – 5.43mg/mL
t - tO 0.50 hour – 0.25 hour e. Assuming the drug is no longer effective
-k0 = 10.32 mg/mL/hour when levels decline to less than 3 mcg/mL,
when should you administer the next dose?
C0 = -k0 t0 + C0
C0 = (10.32 mg/mL/hour)(0.25 hour)+(5.43mg/mL)
C0 = 8.01 mg/mL

## t1/2 = 0.5 CO = 0.5 (8.01 mg/mL)

KO 10.32 mg/mL/hour
1
t /2 = 0.39 hour

## 2. Cp = 45 e -0.17t 3. Cp = 55 e -0.165t + 20 e -0.05t

Dose = 5mg/kg Dose = 50 mg
Px = 70 kg
Dose = 5mg/kg x 70kg = 350mg A = 55 B = 20
Dose = 350 mg x 1000mcg/1mg = 350,000 mcg a = 0.165 b = 0.05

## a. What is t½? Calculate Vp; Vt ; K12 ; K21 ; K

t1/2 = 0.693 = 0.693 (AB = mcg/mL ; ab = hour-1)
k 0.17hr-1
t1/2 = 4.08 hours Vp = __D0___ = 50,000mcg

7
A+B 55+20
Vp = 666.67 mL

Vt = Vp K12 = (666.67mL)(0.0321)
K21 0.0807
Vt = 265.18 mL

K12 = AB (b-a)2___
(A+B)(Ab+Ba)

## K12 = [(55)(20)] [(0.05-0.165)2]

[(55+20)][(55x0.05)(20x0.165)]
K12 = 0.0321 hour-1

K21 = Ab + Ba
(A+B)
K21 = (55)(0.05) + (20)(0.165)
(55+20)
K21 = 0.0807 hour-1

K = ab (A + B)
Ab + Ba
K = [(0.05)(0.165)] [(55 + 20)]
(55)(0.05) + (20)(0.165)
K = 0.1023 hour-1

## 4. What is the Creatinine clearance in a 170

lbs.; Px = 65yrs. Old if the laboratory reports
2.5 mg/dL?

## CrCL = [(140 – age) (Wt. in kg.)]

(72) CrSR
CrCL = [(140-65 yrs. old) (77.27kg)]
(72) (2.5 mg/dL)
CrCL = 32.20 mL/min