Therapeutic drug levels, toxic levels, steady state concentration, half-life

Labs - DRUG Levels (Alphabetical order)

Acetaminophen	Amikacin
Amitriptyline	Carbamazepine
Desipramine	Digoxin
Disopyramide	Ethosuximide
Gentamicin	Imipramine
Lidocaine	Lithium
Nortriptyline	Phenobarbital
Phenytoin	Primidone
Procainamide	Quinidine
Salicylate	Theopylline
Tobramycin	Valproic Acid
Vancomycin

Acetaminophen :

Therapeutic Range: 5-20 mcg/mL

Comments:
Potentially toxic / Critical value:
>150 mcg/mL - Measured 4 hours after the dose.

The ceiling analgesic effect is obtained with a dose of 1 gram (adult).

Rumack-Matthew nomogram for single acute acetaminophen poisoning:
apap toxicity

Recommended reading / References:
Acetadote® (acetylcysteine) Injection. Package insert. Cumberland Pharmaceuticals Inc. Nashville, TN 37203. Feb 2006.

Rumack BH, Matthew M. Acetaminophen poisoning and toxicity. Pediatrics 1975; 55:871–876

Rumack BH, Peterson RC, Koch GG, Amara IA. Acetaminophen overdose: 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med. 1981;141:380-385.

Amikacin:

Therapeutic Range: Peak: 20-30 mcg/ml. Trough: 4-8 mcg/ml

Comments:
Half-life: (average 2-3 hours)

Potentially toxic:
peak: >30.0 mcg/mL,
trough: >8.0 mcg/mL.

Drawing levels: Draw peak 30 minutes after a 30 infusion or 60 minutes after an IM injection. Draw trough just prior to next dose or at least one half-life after the peak.

Amitriptyline

Therapeutic Range: 120 to 150 ng/ml

Comments:
Toxic level: >500 ng/ml
Half-life: 17-40 hours Steady state: 3-8 days.

Drawing levels: draw trough immediately prior to next dose

Carbamazepine

Therapeutic Range: 4 to 12 mcg/ml

Comments:
Toxic level: >12 mcg/ml
Half-life: 10 - 26 hours in adults.

Time to steady state: 2 to 10 days (Possibly 2-4 weeks due to autoinduction.)

Monitoring: draw trough immediately prior to next dose.

Desipramine

Therapeutic Range: 150 to 300 ng/ml

Comments:
Toxic level: >500 ng/ml

Half-life: 12-54 hours

Time to steady state: 6-11 days. Monitoring: obtain trough just prior to next dose.

Digoxin

Therapeutic Range: 0.8 to 2.0 ng/ml

Comments:
Steady state: 7- 10 days (possibly longer).
Toxic level: >2.4 ng/ml

Half-life: 33 - 51 hours.

Obtaining levels: determine serum digoxin levels at least 4 hours after an IV dose or 6 hours after an oral dose in order to allow sufficient time for drug distribution.

Disopyramide

Therapeutic Range: 2 to 5 mcg/ml

Comments:
Toxic level: >5 mcg/ml

Half-life: 5 - 10 hours.

Ethosuximide

Therapeutic Range: 40 to 100 mcg/mL

Comments:
Toxic level: >100 mcg/ml

Half-life: 20 to 60 hours.

TTime to steady state: 7-10 days.

Obtaining levels: peak: 2-4 hours after the dose. Trough: immediately prior to next dose.

Gentamicin

Therapeutic Range:
Conventional dosing: Peak: 4-10 mcg/ml.
Trough: 0.5 to 2 mcg/ml

Comments:
HHalf-life: (average 2-3 hours).

Drawing levels: Draw peak 30 minutes after a 30 infusion or 60 minutes after an IM injection. Draw trough just prior to next dose or at least one half-life after the peak.

Imipramine

Therapeutic Range:: 150 to 250 ng/ml

Comments::
Toxic level: >500 ng/ml
Half-life: 9-24 hours
Steady state: 2-5 days.

Lidocaine

Therapeutic Range:: 1.5 to 5.0 mcg/ml

Comments::
Potentially Toxic level: >5 mcg/ml
Half-life: 1.5 hours
Time to steady state: 6-12 hours.

Lithium

Therapeutic Range:: 0.5 to 1.3 mEq/L

Comments:
Potentially Toxic level: >1.5 mEq/L
Half-life: 17-36 hours.

Drawing levels: just prior to next dose or at least 6-12 hours after the last dose

Nortriptyline

Therapeutic Range:: 50 to 150 ng/ml

Comments::
Toxic level: >500 ng/ml
Half-life: 15-90 hours
Steady state: 4-20 days.

Drawing levels: just prior to next dose

Phenobarbital

Therapeutic Range:: 15 to 40 mcg/ml

Comments::
(Steady state: 15-25 days)
Toxic level: >40 mcg/ml
Half-life: 1.5 - 3 days

Drawing levels: Peak: 4-12 hours after dose.
Trough: immediately prior to next dose

Phenytoin

Therapeutic Range:: Total: 10 to 20 mcg/ml. Free: 1-2 mcg/ml.

Comments::
Toxic level: >20-30 mcg/ml
Half-life: 7-42 hours (average: 24 hours)

Time to steady state: 7-10 days.

Drawing levels:
IV: 2-4 hours after loading dose.
Oral (peak): 3-9 hours after dose (not critical).
Trough: immediately prior to next dose.

Primidone

Therapeutic Range:: 5 to 12 mcg/ml

Comments::
Toxic level: >12 mcg/ml
Half-life: 6 - 12 hours.

Converted into two active metabolites: phenobarbital and phenylethylmalonamide (PEMA).

Procainamide

Therapeutic Range: 4 to 10 mcg/ml. NAPA: 6 - 20 mcg/ml.

Comments:
(Steady state: 12 to 18 hours)
Toxic level: >16 mcg/ml
Half-life: 2.5 - 4.5 hours

Quinidine

Therapeutic Range: 2 to 5 mcg/ml

Comments:
Potentially toxic level: >6 mcg/ml
Half-life: 4-11 hours

Draw trough level: immediately prior to next dose

Salicylate

Therapeutic Range: 50 to 250 mcg/ml (5-25 mg/dL)

Comments:
Potentially toxic level:
>300 mcg/ml (> 30 mg/dL)

Theopylline

Therapeutic Range: (adult): 10 to 20 mcg/ml.

Comments:
Toxic level: >20 mcg/ml
Half-life: 3 -10 hours

Time to steady state: 36 hours (average).

Drawing levels: (after steady state achieved):
a] Oral solution or immediate-release tablet:
1-2 hours after administration.

b] Extended-release tablet:
4-12 hours after administration.

Recheck levels 1-2 days after any dosage change (adults).

THEOPHYLLINE IN DEXTROSE (theophylline anhydrous) injection, solution
[Baxter Healthcare Corporation] Package Insert (accessed 9/16/2014):
In patients who have received no theophylline in the previous 24 hours, a serum concentration should be measured 30 minutes after completion of the intravenous loading dose to determine whether the serum concentration is <10 mcg/mL indicating the need for an additional loading dose or >20 mcg/mL indicating the need to delay starting the constant IV infusion. Once the infusion is begun, a second measurement should be obtained after one expected half-life (e.g., approximately 4 hours in children age 1 to 9 years and 8 hours in nonsmoking adults; See package insert for the expected half-life in additional patient populations). The second measurement should be compared to the first to determine the direction in which the serum concentration has changed. The infusion rate can then be adjusted before steady-state is reached in an attempt to prevent an excessive or sub-therapeutic theophylline concentration from being achieved. If a patient has received theophylline in the previous 24 hours, the serum concentration should be measured before administering an intravenous loading dose to make sure that it is safe to do so. If a loading dose is not indicated (i.e., the serum theophylline concentration is >/=10 mcg/mL), a second measurement should be obtained as above at the appropriate time after starting the intravenous infusion. If, on the other hand, a loading dose is indicated, a second blood sample should be obtained after the loading dose and a third sample should be obtained one expected half-life after starting the constant infusion to determine the direction in which the serum concentration has changed.

Once the above procedures related to initiation of intravenous theophylline infusion have been completed, subsequent serum samples for determination of theophylline concentration should be obtained at 24-hour intervals for the duration of the infusion. The theophylline infusion rate should be increased or decreased as appropriate based on the serum theophylline levels. When signs or symptoms of theophylline toxicity are present, the intravenous infusion should be stopped and a serum sample for theophylline concentration should be obtained as soon as possible, analyzed immediately, and the result reported to the clinician without delay. In patients in whom decreased serum protein binding is suspected (e.g., cirrhosis, women during the third trimester of pregnancy), the concentration of unbound theophylline should be measured and the dosage adjusted to achieve an unbound concentration of 6-12 mcg/mL.

Tobramycin

Therapeutic Range: Conventional dosing: Peak: 4-10 mcg/ml. Trough: 0.5 to 2 mcg/ml.

Comments:
Half-life: (average 2-3 hours).

Drawing levels: Draw peak 30 minutes after a 30 infusion or 60 minutes after an IM injection. Draw trough just prior to next dose or at least one half-life after the peak.

Valproic Acid

Therapeutic Range: 40 to 100 mcg/ml

Comments:
(Steady state: 2-4 days)
Toxic level: >100 mcg/ml
Half-life:
9 - 18 hours in adults.
4 - 14 hours in children

Vancomycin

Therapeutic Range: Peak: 20-40 mcg/ml. Trough: 10 - 20 mcg/ml*^

Comments:

*Minimum trough levels should be maintained above 10 mcg/ml in order to avoid the development of resistance.

^Trough concentrations of 15-20 mcg/ml should be reserved for complicated or deep-seated infections including: bacteremia, endocarditis, hospital-acquired pneumonia, meningitis, and osteomyelitis.

Comments:
Half-life: (average: 6 hours).

Drawing levels:
Draw trough immediately prior to the 4th dose. Peak level monitoring is not recommended (not a reliable indicator of potential nephrotoxicity).

References

Basic Skills in Interpreting Laboratory Data, 5th Ed. (2013) Lee M (editor). American Society of Health-System Pharmacists, ISBN 1585283436.

Drug information handbook: a comprehensive resource for all clinicians and healthcare professionals, 24th Ed. (2015) Lexi-Comp.

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David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.