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Drug Half-Life, Steady State, and Recommended Sample Collection Time

Drug Half-Life, Steady State, and Recommended Sample Collection Time

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Therapeutic Drug Monitoring

Drug Half-Life, Steady State, and Recommended Sample Collection Time

Therapeutic drug monitoring (TDM) is commonly used to help maintain drug levels within the therapeutic window,1,2 the concentration range in which a drug exerts its clinical effect with minimal adverse effects for most patients. TDM is particularly useful for monitoring drugs that are used long-term and have a narrow therapeutic range.1,2 TDM is also useful to detect and monitor drug interactions and identify inadequate adherence as a cause of poor treatment response.1,2

Blood samples are usually collected at steady state to obtain clinically useful serum drug concentrations.1 When a fixed dose is administered at regular intervals, a drug will accumulate in the body during the absorption phase until it reaches steady state, during which the rate of drug intake equals the rate of drug elimination.1 The time required to reach steady state depends on the elimination half-life of the drug, defined as the time required for the serum drug concentration to decrease by 50%. The half-life is itself determined by the metabolism and excretion rates of the drug. Under conditions of first-order kinetics in a one-compartment distribution model (drug is rapidly and evenly distributed throughout the body) and in the absence of a loading dose, at least 5 half-lives are required to achieve a steady state.1,3 However, some drugs are metabolized by non—first-order kinetics, undergo extensive first-pass metabolism in the liver, and/or follow multicompartment distribution in the body (drug is distributed into plasma at one rate then exchanged between plasma and tissues at a different rate).3 The time required for these drugs to reach a steady state may differ from the conventional 5 half-lives. Except in medical emergencies, the monitored drug should be allowed to reach a new steady state following a dosage change and the addition or discontinuation of a co-administered drug.1 Similarly, the same amount of time needs to elapse to almost completely eliminate a discontinued drug that had reached steady state.

Once steady state has been reached, peak and/or trough serum samples may be collected after the next scheduled dose. For peak samples, that would typically be 2 to 3 hours after an oral dose,2 30 to 60 minutes after an intravenous dose,2 2 to 4 hours after an intramuscular dose,2 or 1 to 1.5 hours after an intranasal dose.4,5 Trough samples are drawn just before administration of the next scheduled dose. TDM of aminoglycoside antibiotics, such as gentamicin and amikacin, requires determination of both peak and trough concentrations for multiple daily dosing regimens.3 Only trough concentrations are measured for most other drugs.2

The Table contains, unless otherwise specified, estimates of the elimination half-life and steady state sample collection time for commonly administered drugs (ie, those administered in multiple doses) but excluding time-release and long-acting regimens. The pharmacokinetics of each drug may vary with patient age, sex, weight, clinical status, and the presence of other drugs. These parameters are generalized guidelines and are not meant to replace patient assessment and clinical judgment.

Table. Drug Half-life and Time to Steady Statea

Acetaminophen
Half-Life Time to Steady State
1 - 4 hours6 10 - 20 hours6

Acyclovir

 
Half-Life Time to Steady State
2 - 3 hours Not given

Alprazolam

 
Half-Life Time to Steady State
6 - 16 hours (Adult, <65 years) 5 - 6 days7
9 - 27 hours (Adult, 65 years)

Prolonged in obesity and hepatic disease;
  longer by 25% in Asians vs Caucasians

Amikacin

 
Half-Life Time to Steady State
2 - 3 hours8 (Adult) 15 - 24 hours8 (Adult)
1 - 3 hours8 (Child)

Prolonged in renal disease

5 - 6 hours8 (Child)

Amiodarone

 
Half-Life Time to Steady State
26 - 107 days9 Not applicable

Amitriptyline

 
Half-Life Time to Steady State
8 - 51 hours9 (Amitriptyline) 2 - 6 days6 (Amitriptyline)
15 - 90 hours9 (Nortriptyline) 4 - 21 days6 (Nortriptyline)

Amoxicillin

 
Half-Life Time to Steady State
1 - 2 hours9 2 days10

Amphetamine

 
Half-Life Time to Steady State

7 - 34 hours9 (Urine pH-dependent)

Not given

Amphotericin

 
Half-Life Time to Steady State
15 days Not given

Amprenavir

 
Half-Life Time to Steady State
7 - 11 hours 3 - 4 weeks11

Anidulafungin

 
Half-Life Time to Steady State
40 - 50 hours 24 hours

Argatroban

 
Half-Life Time to Steady State

39 - 51 min12

1 - 3 hours12

Aztreonam

 
Half-Life Time to Steady State

1 - 2 hours (Prolonged in renal disease)

60 hours13

Bismuth

 
Half-Life Time to Steady State

21 - 72 days14 (Terminal half-life)

Not given

Caffeine

 
Half-Life Time to Steady State
3 - 12 hours9 (Adult) Not applicable (high variability)
40 - 230 hours8 (Neonate)

Capreomycin

 
Half-Life Time to Steady State
12 hours Not given

Carbamazepine

 
Half-Life Time to Steady State
14 - 47 hours8 (Adult) 7 - 12 days8 (Adult)
8 - 19 hours6 (Child) 2 - 4 days6 (Child)

Carisoprodol

 
Half-Life Time to Steady State
1 - 3 hours9 Not applicable

Caspofungin

 
Half-Life Time to Steady State
9 - 11 hours Not given

Cefuroxime

 
Half-Life Time to Steady State

1 - 2 hours (Prolonged in renal disease)

5 days15

Cephalexin

 
Half-Life Time to Steady State
50 - 60 min16 2 days17

Chlordiazepoxide

 
Half-Life Time to Steady State

6 - 25 hours14 (Normal)

Not given

5 - 30 hours14 (End-stage renal disease)

30 - 63 hours14 (Liver cirrhosis)

Chlorpromazine

 
Half-Life Time to Steady State
7 - 119 hours9 Not applicable

Ciprofloxacin

 
Half-Life Time to Steady State

4 hours (Slightly prolonged in renal disease)

3 days17

Clarithromycin

 
Half-Life Time to Steady State
3 - 4 hours 3 days

Clindamycin

 
Half-Life Time to Steady State

2 - 4 hours (Slightly prolonged in renal disease)

2 days17

Clomipramine

 
Half-Life Time to Steady State
12 - 36 hours9 3 weeks18

Clonazepam

 
Half-Life Time to Steady State
19 - 60 hours9 7 days19

Clozapine

 
Half-Life Time to Steady State
4 - 66 hours Not applicable

Cycloserine

 
Half-Life Time to Steady State
12 hours Not given

Cyclosporine

 
Half-Life Time to Steady State

6 - 27 hours6 (Influenced by underlying disease)

2 - 6 days6

Delavirdine

 
Half-Life Time to Steady State
2 - 11 hours 2 - 4 weeks20

Desipramine

 
Half-Life Time to Steady State
12 - 54 hours9 Not given

Diazepam

 
Half-Life Time to Steady State

21 - 37 hours9 (Prolonged in hepatic disease)

5 - 14 days21

Dicloxacillin

 
Half-Life Time to Steady State
42 min22 2 days17

Digitoxin

 
Half-Life Time to Steady State
4 - 10 days9 4 weeks23

Digoxin

 
Half-Life Time to Steady State

36 - 48 hours (Prolonged in renal disease)

7 - 10 days6

Disopyramide

 
Half-Life Time to Steady State

4 - 10 hours6 (Prolonged in renal disease)

24 - 48 hours6

Doxepin

 
Half-Life Time to Steady State
8 - 25 hours8 2.5 - 5 days6

Doxycycline

 
Half-Life Time to Steady State
18 - 22 hours Not given

Efavirenz

 
Half-Life Time to Steady State
40 - 55 hours 4 weeks24

Ethambutol

 
Half-Life Time to Steady State
24 hours Not given

Ethosuximide

 
Half-Life Time to Steady State
50 - 60 hours6 (Adult) 8 - 12 days6 (Adult)
30 hours6 (Child) 6 - 10 days6 (Child)

Everolimus

 
Half-Life Time to Steady State
26 - 38 hours9

Not given

Felbamate

 
Half-Life Time to Steady State

11 - 23 hours9 (Prolonged in renal disease)

5 days25

Fentanyl

 
Half-Life Time to Steady State
3 - 12 hours9

Not given

Flecainide

 
Half-Life Time to Steady State

12 - 27 hours9 (Prolonged in renal disease)

3 - 6 days26

Fluconazole

 
Half-Life Time to Steady State

20 - 50 hours (Adult)

10 days27

15 - 25 hours (Child)

74 hours (Premature neonate)

Prolonged in renal disease

Flucytosine (5FC)

 
Half-Life Time to Steady State
3 - 5 hours (Adult) 18 - 30 hours28

8 hours (Child)

Prolonged in renal disease

Fluoxetine

 
Half-Life Time to Steady State
4 - 6 days 4 weeks29
Fluphenazine
Half-Life Time to Steady State
13 - 58 hours9 (Hydrochloride) 2 weeks30
3 - 4 days9 (Enanthate)
5 - 12 days9 (Decanoate)

Fondaparinux

 
Half-Life Time to Steady State
17 - 21 hours31 (Prolonged in renal disease) 3 hours31

Gabapentin

 
Half-Life Time to Steady State
5 - 7 hours6 (Adult) 1 - 2 days6 (Adult)
4 - 6 hours6 (Child) 1 - 2 days6 (Child)

Ganciclovir

 
Half-Life Time to Steady State

3 - 6 hours

Not given

Gentamicin

 
Half-Life Time to Steady State

1 - 3 hours9 (Prolonged in renal disease)

1 day32

Haloperidol

 
Half-Life Time to Steady State
14 - 41 hours9 (Lactate) 3 - 9 daysb (Lactate)
14 - 28 days9 (Decanoate) Not applicable (Decanoate)

Heparin Anti-Xa (Low Molecular Weight Heparin)

 
Half-Life Time to Steady State

3 - 6 hours31 (Subcutaneous injection)

Prolonged in renal disease

2 - 4 days (Enoxaparin sodium)

Heparin Anti-Xa (Unfractionated Heparin)

 
Half-Life Time to Steady State
30 - 150 min31(Dose dependent) 6 hours31

10-Hydroxycarbazepine

 
Half-Life Time to Steady State
8 - 15 hours6 2 days6

Imipramine

 
Half-Life Time to Steady State
6 - 20 hours9 (Imipramine) 2 - 5 days6 (Imipramine)
12 - 54 hours9 (Desipramine)

Indinavir

 
Half-Life Time to Steady State

1 - 3 hours (Prolonged in hepatic disease)

2 weeks33

Isoniazid

 
Half-Life Time to Steady State
1 - 2 hours9 (Adult, slow inactivator
  [50% of blacks and Caucasians])
6 - 8 weeks34,35
2 - 7 hours9 (Adult, rapid inactivator
  [majority of Asians and Inuit])
 

Itraconazole

 
Half-Life Time to Steady State
14 - 18 hours 15 days

Ketoconazole

 
Half-Life Time to Steady State
2 - 8 hours Not given

Lacosamide

 
Half-Life Time to Steady State
13 hours14 Not given

Lamotrigine

 
Half-Life Time to Steady State
15 - 30 hours6 (Adult) 3 - 10 days6 (Adult)
~30 hours6 (Child) 3 - 10 days6 (Child)

Leflunomide

 
Half-Life Time to Steady State
14 - 18 days14 Not given

Levetiracetam

 
Half-Life Time to Steady State
6 - 8 hours6 (Adult) 2 days6 (Adult)

5 - 7 hours6 (Child)

Prolonged in renal disease

1 - 2 days6 (Child)

Lidocaine

 
Half-Life Time to Steady State

1 - 2 hours6 (Prolonged in hepatic disease)

8 - 10 hours6

Lithium

 
Half-Life Time to Steady State

14 - 30 hours6 (Varies with renal function)

2 - 7 days6

Lopinavir/Ritonavir

 
Half-Life Time to Steady State
4 - 5 hours (Lopinavir) 3 - 4 weeks36 (Lopinavir)

Maprotiline

 
Half-Life Time to Steady State
36 - 105 hours9 14 days9

Meperidine

 
Half-Life Time to Steady State
2 - 5 hours9 Not given

Mephobarbital

 
Half-Life Time to Steady State
48 - 52 hours9 Not given

Meprobamate

 
Half-Life Time to Steady State
6 - 17 hours9 Not given

Methotrexate

 
Half-Life Time to Steady State

3 - 10 hours9 (Psoriasis, rheumatoid arthritis, or

low dose)

Not given

8 - 15 hours9 (High dose therapy)

Metronidazole

 
Half-Life Time to Steady State

8 hours (Prolonged in hepatic disease)

2 days37

Methylphenidate

 
Half-Life Time to Steady State
2 - 5 hours9 (Adult) Not applicable
2 - 3 hours9 (Child)

Minocycline

 
Half-Life Time to Steady State

12 - 25 hours (Prolonged in renal disease)

3 days38

Morphine

 
Half-Life Time to Steady State
1 - 7 hours9 Not given

Mycophenolic Acid

 
Half-Life Time to Steady State
8 - 18 hours6 (Adult) Not applicable

Variable6 (Child)

Mycophenolic acid glucuronide

Influenced by underlying disease

Nelfinavir

 
Half-Life Time to Steady State
4 - 5 hours 2 weeks39

Nevirapine

 
Half-Life Time to Steady State
25 - 30 hours 4 weeks40

Norfentanyl

 
Half-Life Time to Steady State
Not applicable

Inactive metabolite; see fentanyl

1-3 days41 (Urine detection)

Nortriptyline

 
Half-Life Time to Steady State
18 - 93 hours6 4 - 21 days6

Olanzapine

 
Half-Life Time to Steady State
21 - 54 hours (Adult, 65 years) 7 days42
32 - 81 hours (Adult, >65 years)

Oxcarbazepine

 
Half-Life Time to Steady State

1 - 2 hours (Unchanged drug)

Not applicable (Unchanged drug)

9 hours (Active monohydroxy metabolite)

2 - 3 days (Metabolite)

Oxycodone

 
Half-Life Time to Steady State
3 - 5 hours43 Within 24 hours43

Paroxetine

 
Half-Life Time to Steady State
7 - 37 hours9 10 days24

Pentobarbital

 
Half-Life Time to Steady State
20 - 30 hours9 (Dose dependent) Not applicable

Phenolphthalein

 
Half-Life Time to Steady State
Dependent on catharsis Not applicable

Phenobarbital

 
Half-Life Time to Steady State
81 - 117 hours6 (Adult) 17 - 24 days6 (Adult)
40 - 70 hours6 (Child) 8 - 15 days6 (Child)
Phenytoin
Half-Life Time to Steady State
18 - 22 hours6 (Adult, therapeutic dose) 4 - 8 days6 (Adult, therapeutic dose)
7 - 29 hours6 (Child) 2 - 5 days6 (Child)

Dose dependent

Posaconazole
Half-Life Time to Steady State
32 - 37 hours 7 - 10 days
Pregabalin
Half-Life Time to Steady State
6 hours44 1 - 2 days44

Primidone

 
Half-Life Time to Steady State
3 - 7 hours6 (Adult) 16 - 60 hours6 (Adult)
4 - 6 hours6 (Child) 20 - 30 hours6 (Child)

Procainamide

 
Half-Life Time to Steady State
2 - 5 hours6 11 - 20 hours6

6 hours9 (N-acetyl procainamide)

Not applicable (N-acetyl procainamide)

Propafenone

 
Half-Life Time to Steady State
2 - 10 hours (Normal metabolizer
  [>90% of population])
4 - 5 days45

10 - 32 hours (Slow metabolizer
  [<10% of population])

Prolonged in hepatic disease

Propranolol

 
Half-Life Time to Steady State
2 - 6 hours6 Not applicable

Pyrazinamide

 
Half-Life Time to Steady State

10 hours (Prolonged in renal disease)

6 - 8 weeks34,35

Quinidine

 
Half-Life Time to Steady State
5 - 9 hours6 (Adult) 30 - 35 hours6 (Adult)
3 - 7 hours6 (Child) Varies with age6 (Child)

Rifabutin

 
Half-Life Time to Steady State
16 - 69 hours Not given

Rifampin

 
Half-Life Time to Steady State
2 - 3 hours 6 - 8 weeks34,35

Risperidone

 
Half-Life Time to Steady State

3 hours (Fast metabolizer, risperidone)

1 day26 (Fast metabolizer, risperidone)

21 hours (Fast metabolizer, 9-hydroxy-risperidone)

5 - 6 days26 (Fast metabolizer, 9-hydroxy risperidone)

20 hours (Slow metabolizer, risperidone)

5 days26 (Slow metabolizer, risperidone)

30 hours (Slow metabolizer, 9-hydroxy-risperidone)

Prolonged in renal disease

Not applicable (Slow metabolizer, 9-hydroxy-risperidone)

Ritonavir

 
Half-Life Time to Steady State
3 - 5 hours 3 - 4 weeks46

Salicylate

 
Half-Life Time to Steady State
2 - 3 hours6 (Adult, therapeutic dose) 10 - 23 hours6 (Adult, therapeutic dose)
20 hours (Adult, toxic doses) Not applicable (Adult, toxic doses)

Saquinavir

 
Half-Life Time to Steady State
12 hours47 4 weeks48

Secobarbital

 
Half-Life Time to Steady State
22 - 29 hours9 Not applicable

Sirolimus (rapamycin)

 
Half-Life Time to Steady State

46 - 78 hours6 (Influenced by underlying disease)

5 - 7 days6

Streptomycin

 
Half-Life Time to Steady State
5 - 6 hours Not given

Sulfamethoxazole

 
Half-Life Time to Steady State

10 hours  (Prolonged in renal disease)

2 days17

Tacrolimus (FK506)

 
Half-Life Time to Steady State
4 - 35 hours6 (Adult) 2 - 6 days6 (Adult)

4 - 12 hours6 (Child)

Influenced by underlying disease

Not applicable (Child)

Tetracycline

 
Half-Life Time to Steady State
7 - 11 hours9 2 - 3 days49.

Theophylline

 
Half-Life Time to Steady State
7 - 11 hours6 (Adult, 16 - 60 years) 15 - 55 hours6 (Adult, 16 - 60 years)

1 - 8 hours6 (Child, 1 - 17 years)

Influenced by underlying disease

5 - 40 hours6 (Child, 1 - 17 years)

Thiocyanate

 
Half-Life Time to Steady State

<2 min14(Nitroprusside)

Thiocyanate is a metabolite of nitroprusside therapy

and cyanide poisoning

Not applicable

Tobramycin

 
Half-Life Time to Steady State

2 hours

1 - 2 days50

Topiramate

 
Half-Life Time to Steady State

19 - 23 hours9 (Prolonged in renal disease;

reduced in pediatric patients aged 4-17 years)

5 days51

Trazodone

 
Half-Life Time to Steady State
4 - 7 hours9  4 days6

Trimethoprim

 
Half-Life Time to Steady State

8 - 10 hours (Prolonged in renal disease)

2 days17

Trimipramine

 
Half-Life Time to Steady State
16 - 39 hours9 Not applicable

Valproic Acid

 
Half-Life Time to Steady State
9 - 16 hours (Adult) 2 - 4 days6 (Adult)

7 - 13 hours (Child, 3 months - 10 years)

Prolonged in hepatic disease

2 - 4 days6 (Child, 3 months - 10 years)

Vancomycin

 
Half-Life Time to Steady State
3 - 8 hours9 1 - 2 days50

Voriconazole

 
Half-Life Time to Steady State
6 - 9 hours14, 52-54 (Increases with dose) 5 - 7 days14, 52-54

Warfarin

 
Half-Life Time to Steady State

20 - 60 hours (Prolonged in poor metabolizers)

5 - 13 daysb

Zonisamide

 
Half-Life Time to Steady State
53 - 75 hours9 14 days55
a Data listed are for adults, unless otherwise specified. Unless otherwise referenced, data were obtained from the drug prescribing information.

b Time to steady state was calculated by multiplying the half-life by 5.

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Content reviewed 04/2013
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