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THERAPEUTIC DRUG MONITORING

 

PATIENT DATA/BACKGROUND:

Please provide some guidelines on when to draw serum levels and the therapeutic ranges for the aminoglycosides, cyclosporine, vancomycin, lithium, quinidine, digoxin, procainamide, chloramphenicol, quinidine, and the antiepileptics.

RESPONSE:

Therapeutic drug monitoring is the process of using drug concentrations, pharmacokinetic principles, and pharmacodynamic criteria to optimize drug therapy in individual patients. Optimization is primarily accomplished by minimizing the potential for toxicity and increasing the probability of the desired therapeutic effect. Misconceptions exist surrounding the use of therapeutic ranges such as the assumption that the therapeutic ranges for most drugs have been well defined from controlled clinical trials. Another misconception is that concentrations in the therapeutic range will always result in the desired clinical response. A therapeutic range should never be considered in absolute terms (Evans et al, 1986).

A variety of factors exist which influence the interpretation of drug levels: time, route, and dose of the drug, the time levels are obtained, handling and storage conditions of samples, precision and accuracy of the analytical method, validity of pharmacokinetic models and assumptions, concurrent drug therapy, and the individual's disease state (or other concurrent disease states) and biological tolerance to drug therapy (Evans et al, 1986).

The prerequisites for the usefulness of drug concentrations in routine patient care include a narrow therapeutic index, significant consequences associated with therapeutic failure or toxicity, wide interpatient pharmacokinetic variability, and the usefulness of drug concentrations to monitor and aid in therapeutic decisions (Evans et al, 1986).

 

AMINOGLYCOSIDES 

THERAPEUTIC RANGE FOR AMINOGLYCOSIDES
   (Dudley, 1989; Evans et al, 1986; Knoben & Anderson, 1988)

DRUG

PEAK

TROUGH

Soft Tissue and other less severe Infections

Life Threatening Infections

Soft Tissue and other less severe Infections

Life Threatening Infections

Amikacin
(click) 

12-16 mcg/mL

25-35 mcg/mL

1-4 mcg/mL

Less than 10 mcg/mL

Netilmicin
(click)

5-8 mcg/mL

8-10 mcg/ml

1 mcg/mL

1-2 mcg/mL

Gentamicin
(click)

5-8 mcg/mL

8-10 mcg/mL

1 mcg/mL

1-2 mcg/mL

Tobramycin
(click)

5-8 mcg/mL

8-10 mcg/mL

1 mcg/mL

1-2 mcg/mL

ELIMINATION HALF-LIFE: 
Normal renal function: 2-3 hours  (Strongly dependent on renal function) 
VOLUME OF DISTRIBUTION:  0.25 liter/kilogram 
PHARMACOKINETIC MODEL:  linear; 2 compartment*, with significant distribution               
                         phase (Evans et al, 1986; Winters, 1988). 
                      *Patients in renal failure may exhibit 3 compartment        
                       pharmacokinetics (Evans et al, 1986). 
TIMING OF SAMPLES  (under steady state conditions): 
           Peak:   1 hour after initiation of a 30-minute infusion.  Generally, 
                   an acceptable infusion time ranges from 20 to 40 minutes; 
                   however, if an infusion time is greater than 40 minutes, 
                   peak levels should be obtained 30 minutes after the 
                   completion of an infusion (Winters, 1988).* 
           Trough: immediately prior to the next dose 
                   (Evans et al, 1986; Dudley, 1989). 

* Some clinicians recommend the collection of blood samples 1 hour after the initiation of a 15- to 45-minute intravenous infusion to allow for the completion of the distribution phase (Dudley, 1989).

INTERPRETATION OF LEVELS: 

The relationship between serum aminoglycoside concentration and toxicity has been controversial. A higher risk of oto- and nephrotoxicity has generally been associated with elevated peak and trough serum concentrations (Dudley, 1989; Evans et al, 1986). For GENTAMICIN, TOBRAMYCIN, and NETILMICIN, the risk of ototoxicity and nephrotoxicity is elevated if peak concentrations are consistently maintained above 12 to 14 mcg/mL. For AMIKACIN, peak concentrations above 32 to 34 mcg/mL have been associated with a higher risk of oto- and nephrotoxicity (Evans et al, 1986). For GENTAMICIN, tobramycin, and netilmicin trough levels greater than 2 mcg/mL have been associated with a higher incidence of ototoxicity and nephrotoxicity. Trough levels exceeding 8 to 10 mcg/mL for amikacin are associated with a higher risk of toxicity (Dudley, 1989; Evans et al, 1986). Peak and trough serum levels should only be utilized as guidelines, not as absolute values.

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ANTIEPILEPTIC AGENTS: 
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CARBAMAZEPINE:(click for more information) 
THERAPEUTIC RANGE:      4 to 12 mcg/mL (Bauer, 1989; Garnett, 1989; 
                                   Evans et al, 1986; Lott,1988). 
ELIMINATION HALF-LIFE:  15 hours at steady state (Winters,1988) 
VOLUME OF DISTRIBUTION: 1.4 liters/kilogram (Winters, 1988) 

INTERPRETATION:

Optimal serum concentrations of carbamazepine vary considerably between patients (Bauer, 1989; Garnett, 1989; Evans et al, 1986; Lott, 1988). Once steady state has been achieved, plasma samples may be obtained any time relative to the dose. Due to auto-induction of metabolism the half-life will change during the first few weeks of therapy. Plasma levels drawn during the initiation of therapy may be useful in determining a relationship between patient response and concentration, but they may not be useful in predicting the long-term response of plasma levels to a particular dose (Winters, 1988).

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ETHOSUXIMIDE:(click for more information) 
THERAPEUTIC RANGE:  40 to 100 mcg/mL (Bauer, 1989; Garnett, 1989;

                                                Lott, 1988; Evans et al, 1986). 
ELIMINATION HALF-LIFE: 
                      Adult:  50 hours 
                      Child:  30 hours (Winters, 1988) 
VOLUME OF DISTRIBUTION:  0.7 liter/kilogram (Winters, 1988) 
TIMING OF SAMPLES:  trough levels are suggested for consistency, but not 
                       crucial because of the long half-life (Winters, 1988) 

INTERPRETATION: 

Steady state will generally be attained in 7 to 10 days after the maintenance dose has been established. Many patients with absence seizures respond at a concentration in the 125 to 150 mcg/mL range.

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PHENOBARBITAL:(click for more information) 
THERAPEUTIC RANGE:  10 to 25 mcg/mL (possibly up to 40 mcg/mL) 
                    (Bauer, 1989; Garnett, 1989; Lott, 1988) 
ELIMINATION HALF-LIFE:  5 days (Winters, 1988) 
VOLUME OF DISTRIBUTION:  0.7 liter/kilogram (Winters, 1988) 
PHARMACOKINETIC MODEL:  3 compartments (Evans et al, 1986) 
TIMING OF SAMPLES:  just prior to the next dose, but timing is not critical 
                     (Evans et al, 1986;Winters, 1988); however, if 
                     administered intravenously the sample should be taken at 
                     least 1 hour after infusion avoid the distribution phase
                     (Winters, 1988). 

INTERPRETATION:

Serum concentrations of phenobarbital will reach steady state about 20 to 30 days after initiation of therapy. At that time, serum levels should be checked and the patient reassessed. Although it is ideal to measure the concentration just prior to each daily dose, phenobarbital's half-life is so long, daily fluctuations are minor; therefore, serum levels may be obtained at any convenient time (Evans et al, 1986). Plasma levels drawn in the first 1 to 2 weeks of therapy are not useful for predicting the eventual steady state concentrations

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PHENYTOIN:(click for more information)  
THERAPEUTIC RANGE: 10 to 20 mcg/mL (Evans et al, 1986; Garnett,1989;Lott, 1988) 
ELIMINATION HALF-LIFE:  varies with plasma concentration (Winters, 1988). 
VOLUME OF DISTRIBUTION:  0.65 liter/kilogram (Winters, 1988). 
PHARMACOKINETIC MODEL:  nonlinear (capacity limited metabolism)
                              (Evans et al, 1986) 
TIMING OF DOSE:  just prior to the next dose (Evans et al, 1986; Garnett, 1989; 
                                               Lott, 1988) 

INTERPRETATION:

There are a few patients who are seizure free with concentrations below 10 mcg/mL, therefore, clinical evaluation of the patient should also be considered when interpreting serum levels (Evans et al, 1986; Garnett, 1989; Lott, 1988). Trough levels are generally used to monitor therapy. Peak phenytoin levels may be helpful in a patient who may be experiencing side effects (Garnett, 1989).

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VALPROIC ACID:(click for more information) 
THERAPEUTIC RANGE: 30 to 100 mcg/mL (possibly up to 150 mcg/mL or greater) 
                   (Bauer, 1989; Garnett, 1989;Lott, 1988; Evans et al, 1986).
ELIMINATION HALF-LIFE: 
                      Adult:  10 to 12 hours 
                      Child:  6 to 8 hours (Winters, 1988).
VOLUME OF DISTRIBUTION:  0.14 liter/kilogram (ranges between 0.1 and 0.5 L/kg) 
                         (Winters, 1988). 
PHARMACOKINETIC MODEL:  2 compartments, rapid distribution phase
                            (Evans et al, 1986) 
TIMING OF SAMPLES:  prior to the next dose (Winters, 1988;  Evans et al, 1986). 

INTERPRETATION:

Plasma concentrations of valproic acid should be drawn 2 to 4 days after initiating therapy or changing therapy (adding other antiepileptic drugs, changing the dose) (Winters, 1988). Valproic acid concentrations may vary up to 100% over a single dosing interval. Therefore valproic acid levels should be taken at the same time in relationship to dosing. The optimal time would be just prior to the morning dose, but this is not always practical (Evans et al, 1986).

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CARDIAC DRUGS
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DIGOXIN:(click for more information)   
THERAPEUTIC RANGE:  0.5 to 2 ng/mL (Bauer, 1989; Evans et al, 1986). 
ELIMINATION HALF-LIFE:  2 days (Winters, 1988) 
VOLUME OF DISTRIBUTION:  7.3 liters/kilogram (Winters, 1988) 
PHARMACOKINETIC MODEL:  2 compartments (Winters, 1988) 
TIMING OF SAMPLES:  at least 6 to 8 hours after the dose 
                    (preferably 12 to 24 hours)  (Evans et al,1986). 
INTERPRETATION:  

Any adjustment in dose requires a period 4 to 5 times the half-life (8 to 10 days) before new steady state conditions are achieved (Evans et al, 1986).

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PROCAINAMIDE:(click for more information) 
THERAPEUTIC RANGE: 
       Ventricular arrhythmias: 4 to 10 mg/L (Auriccho,1988;Evans et al, 1986). 
ELIMINATION HALF-LIFE:  3.3 hours (Evans et al, 1986) 
VOLUME OF DISTRIBUTION:  2 liters/kilogram (Evans et al, 1986) 
PHARMACOKINETIC MODEL:  2 compartments (Evans et al, 1986) 
TIMING OF SAMPLES: 
      Oral: prior to the next dose 
      Intravenous (using the 2-infusion technique): 
            2 and 12 hours after starting therapy and every 24 hours thereafter 
                      (Evans et al, 1986). 

INTERPRETATION:

In patients with normal renal function steady state procainamide levels are attained 12 to 18 hours after initiating oral therapy. Some patients, particularly those with ventricular tachycardia associated with chronic heart disease may require and tolerate higher procainamide concentrations of 10 to 20 mg/L (these guidelines do not include the use of NAPA levels). The 2-infusion technique for the intravenous administration of procainamide was designed to rapidly and safely attain plasma procainamide levels in the range of 4 to 8 mg/L (a loading infusion over 1 hour followed by a maintenance infusion). (Evans et al, 1986).

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QUINIDINE:(click for more information) 
THERAPEUTIC RANGE (assay method dependent): 
       Nonspecific assays (protein precipitation method):  3 to 8 mcg/mL 
       Specific assays (thin layer chromatography or high performance liquid 
           chromatography): 1 to 4 mcg/mL (Auricchio, 1988; Evans et al, 1986).
ELIMINATION HALF-LIFE:  7 hours (Winters, 1988) 
VOLUME OF DISTRIBUTION:  2.7-3 liters/kilogram (Winters, 1988) 
PHARMACOKINETIC MODEL:  2 compartments (Evans et al, 1986) 
TIMING OF SAMPLES:   prior to dose (Winters, 1988) 

INTERPRETATION:

A plasma concentration should be drawn at least 24 hours after initiating quinidine therapy, unless signs of toxicity develop. If toxicity appears, a plasma level will assist in determining if the dose should be reduced or held (Winters, 1988). The range of therapeutic efficacy for quinidine is highly dependent on the specificity of the assay used and by the presence of active metabolite(s). The therapeutic range for quinidine when determined with a relatively nonspecific assay is generally higher and wider than ranges that are determined by more specific procedures (Auricchio, 1988; Evans et al, 1986).

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CHLORAMPHENICOL:(click for more information)   
THERAPEUTIC RANGE:  10 to 25 mcg/mL (Dudley, 1989; Evans et al, 1986). 
ELIMINATION HALF-LIFE: 
           Adult:  2.25-5.1 hours 
           Child:  1.61-10.1 hours 
           (Evans et al, 1986) 
VOLUME OF DISTRIBUTION: 
           Adult:  0.55-0.92 liter/kilogram 
           Child:  0.63-1.55 liter/kilogram 
                   (Evans et al, 1986) 

TIMING OF SAMPLES: 
   Oral: peak level 1.5 to 3 hours after dose 
   Intravenous: peak level 0.5 to 1.5 hours after the completion of a 30-minute 
                intravenous infusion (Dudley, 1989; Evans et al, 1986). 

INTERPRETATION

In an adult, monitoring of chloramphenicol levels should start 12 to 24 hours after starting therapy; in an infant after 2 to 3 days (Evans et al, 1986). No data exist to correlate serum concentrations to efficacy (Bauer, 1989; Dudley, 1989; Evans et al, 1986). The infusion method and repeated therapy should be taken into account when monitoring chloramphenicol concentrations. Inter- and intrapatient variation in chloramphenicol pharmacokinetics and a narrow therapeutic index support the need to individualize chloramphenicol therapy. Peak concentrations following the administration of chloramphenicol succinate intravenously may be variable due to variable rates of hydrolysis, rates of administration, and the site of infusion (Dudley, 1989; Evans et al, 1986).

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CYCLOSPORINE:(click for more information) 
THERAPEUTIC RANGE: 
      Polyclonal Radioimmunoassay:  300 to 800 ng/mL 
      High Performance Liquid Chromatography:  100 to 150 ng/mL 
      Monoclonal Radioimmunoassay:  95 to 205 ng/mL 
                      (McMillan, 1989) 
ELIMINATION HALF-LIFE:  19 hours (Prod Info Sandimmune(R),1991) 
VOLUME OF DISTRIBUTION: 3.5 to 13 liters/kilogram 
                       (Tech Info Sandimmune(R), 1991) 
PHARMACOKINETIC MODEL:  linear at therapeutic doses (may Exhibit nonlinear 
                     characteristics at toxic blood levels) (Evans et al, 1986) 
TIMING OF SAMPLES: just prior to dose on a 12- or 24-hour  Dosing interval 
                     (Evans et al, 1986; Draxler & Canafax, 1988) 

INTERPRETATION:

Blood levels should be monitored 2 to 3 times during the first few weeks of therapy or if the route of administration is changed (Draxler & Canafax, 1988; Evans et al, 1986). After several months, stable patients can be monitored less frequently. After cyclosporine has reached steady state, trough concentrations yield the most useful information for therapeutic monitoring (Evans et al, 1986). The therapeutic range of cyclosporine levels vary according to the assay technique used. The polyclonal radioimmunoassay (RIA) method is less specific for cyclosporine than high performance liquid chromatography (HPLC). Metabolites of cyclosporine are also detected by polyclonal RIA. Polyclonal RIA may be faster and easier to use than HPLC. Monoclonal RIA is more specific for cyclosporine than monoclonal RIA; however, it has not been used clinically as commonly as the other two methods. Cyclosporine levels should be monitored in whole blood because cyclosporine is significantly bound to the cellular component of blood and plasma cyclosporine levels are subject to change with varying temperature (McMillan, 1989; Rodighiero, 1989). A diurnal variation in the clearance of cyclosporine appears to exist, therefore the concentration of this agent should be monitored at a specific time of the day (Draxler & Canafax, 1988). A technique for monitoring cyclosporine therapy by measuring the area under the plasma concentration-time curve has been studied (Grevel et al, 1989; Grevel & Kahan, 1991). However, this technique requires a large number of venipunctures and assays for each dosing period which may not be practical for many clinical settings.

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LITHIUM:(click for more information)  
THERPAEUTIC RANGE: 0.3 to 1.3 mEq/L (Evans et al, 1986) 
ELIMINATION HALF-LIFE:  20 hours (Winters, 1988) 
VOLUME OF DISTRIBUTION:  0.7 liter/kilogram (Winters, 1988) 
PHARMACOKINETIC MODEL:  linear, 2 compartment (Winters, 1988) 
TIMING OF SAMPLES:  in the morning before the dose is taken
                    and at least 12 hours after the evening
                    dose (Evans et al, 1986) 

INTERPRETATION:

Samples should be obtained under steady state conditions (therapy constant for at least 7 days). However, the therapeutic effect may not appear for 14 to 21 days (Winters, 1988). Controversy surrounds the therapeutic range of lithium due to a lack of standards of blood test sampling (Evans et al, 1986). For treating acute episodes, some clinicians have recommended lithium levels of 0.8 to 1.5 mEq/L and 0.6 to 1.2 mEq/L for maintenance. Initially, lithium levels should be monitored every 4 to 7 days during titration and every 1 to 3 months thereafter (Saklad & Kastenholz, 1988).

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THEOPHYLLINE:(click for more information) 

THERAPEUTIC RANGE:  10 to 20 micrograms/milliliter (peak serum concentration) to prevent   
                                   symptoms and decrease the need for rescue therapy in patients with chronic   
                                   asthma on theophylline monotherapy (Weinberger & Hendeles, 1996).  
                                   However, some patients may experience relief with lower concentrations  
                                   (Weinberger & Hendeles, 1996).
ELIMINATION HALF-LIFE: 54 to 76 hours, premature neonates ; 1.2 to 7 hours, children ; 6 to 12 
                                    hours, adults
VOLUME OF DISTRIBUTION (Vd): 450 mL/kg (Hendeles et al, 1995; Koup et al, 1976; Levy et al, 
                                                                                                                                    1974)
TIME TO PEAK SERUM CONCENTRATION (Weinberger & Hendeles, 1996): (1) Slo-bid Gyrocap 
                                   capsule- 3 to 7 hours after morning dose when given every 12 hours. (2) 
                                   Theo-24 capsul Variable depending on whether taken in the morning after an 
                                   overnight fast, after breakfast, or in the evening. (3) Theo-Dur tablet- 3 to 7 
                                   hours after morning dose when given every 12 hours. (4) Uni-Dur tablet- 8 to
                                   12 hours after once-daily evening dose. (5) Uniphyl tablet- 8 to 12 hours after 
                                   once-daily evening dose.
  Repeat serum concentrations every 6 to 12 months. More frequent intervals may be necessary if the patient's condition is unstable or factors that alter elimination are present (Prod Info Slo-Phyllin(R) tablets and syrup, 2000; Prod Info Theolair-SR theophylline sustained- release tablets, 2000; Prod Info Slo-bid Gyrocaps theophylline extended release capsules, 2000; Prod Info SloPhyllin GG theophylline- guaifenesin syrup, 2000).
  Only use results from laboratories that measure serum levels in duplicate. If results are inconsistent with the clinical situation, repeat the measurement before increasing the dose (Hendeles & Weinberger, 1983).
PATIENT DATA/BACKGROUND:
       When and how often should serum theophylline concentrations be measured?
RESPONSE:
Serum theophylline levels are an invaluable monitoring tool in theophylline dosing. Dosing of theophylline may be complicated due to the extensive variation in bioavailability among patients. Theophylline has a relatively low therapeutic index. Therefore, appropriate dosing is critical, and should be based on patient response and tolerance, pulmonary function, and serum theophylline concentrations (AHFS, 1990).
In general, therapeutic serum theophylline concentrations range from 5 to 15 ug/mL. Toxicity usually appears at concentrations above 20 ug/mL. Peak theophylline levels are better correlated with efficacy and toxicity than trough levels (Kelly & Smith, 1988; Hendeles et al, 1986). The recommended time to obtain a peak serum theophylline concentration level after an initial intravenous aminophylline dose is 30 minutes after completion of the loading dose (Anon, 1995). For an orally administered theophylline solution or uncoated tablet and extended-release theophylline preparations, 1 to 2 hours and 3 to 12 hours after the initial dose, respectively, is recommended (AHFS, 1990; Hendeles et al, 1986). The manufacturers of once-a-day theophylline preparations recommend obtaining peak theophylline serum concentration levels at 12 hours and 8 to 12 hours after a dose of Theo-24(R) and Uniphyl(R), respectively (Kelly & Smith, 1988). Trough levels may be obtained just prior to the next dose of theophylline (AHFS, 1990), however these levels do not generally provide any clinical relevant information (Hendeles et al, 1986). On each occasion, blood samples should be obtained during the same dosing interval to minimize the circadian variation in theophylline absorption.
Patients receiving an intravenous loading dose and continuous theophylline infusion according to general dosing guidelines should have theophylline levels obtained at the following times: 30 minutes after completion of the initial loading dose; once the continuous infusion is initiated, a second level drawn after one expected half-life (8 hours in non-smoking adults and 4 hours in children age 1 to 9 years); and 12 to 24 hours after any dose modification of the continuous infusion. Subsequently, daily serum theophylline concentrations should be obtained once the patient is stabilized on continuous theophylline infusion (Anon, 1995; Kelly & Smith, 1988).
Yearly serum theophylline concentrations are recommended for adult patients receiving oral maintenance theophylline preparations. Pediatric patients, especially during growth phases, should have theophylline levels checked every 6 months. Additionally, serum theophylline concentrations should be obtained when the patient's physiology, disease state, or pulmonary function changes, or if the patient is experiencing theophylline-related side effects (Kelly & Smith, 1988; Hendeles et al, 1986).
In patients in whom reductions in protein binding occur (premature neonates, elderly, patients with hepatic cirrhosis, uncorrected acidemia, and women in their third trimester of pregnancy), measurement of unbound serum theophylline concentrations provides a more accurate means of dosage adjustment and assessment (Anon, 1995). The recommended range for unbound theophylline concentration is 6 to 12 mcg/mL.
CONCLUSION:
Appropriate theophylline dosing is essential due to low therapeutic index and variable patient-to-patient bioavailability. Obtaining serum theophylline concentration levels allows for accurate dosing and is one of several necessary monitoring parameters in theophylline therapy. Consideration should be given to monitoring unbound serum theophylline concentrations in patients in whom decreased serum protein binding is suspected.

End of Document

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VANCOMYCIN:(click for more information) 
THERAPEUTIC RANGE: 
     Peak serum concentration: 25 to 40 mg/L 
     Trough serum concentration: 5 to 10 mg/L 
     (Dudley, 1989; Matzke & Flaherty, 1988; Matzke & Kovarik, 1988). 
ELIMINATION HALF-LIFE:  6-10 hours (Winters, 1988) 
VOLUME OF DISTRIBUTION:  0.7 liter/kilogram (ranges from 0.5 to 1 L/kg) 
                        (Winters, 1988) 
PHARMACOKINETIC MODEL:  2 or 3 compartments (Winters, 1988;  Evans et al, 1986) 
TIMING OF SAMPLES: 
    Peak:  at least 1 hour after the discontinuation of an infusion 
    Trough: just before or within 1 hour of the next scheduled dose 
             (Dudley, 1989; Matzke & Flaherty, 1988;Matzke & Kovarik, 1988) 

INTERPRETATION:

The therapeutic range for vancomycin peak and trough concentrations were derived primarily from observations that, at these concentrations toxicity typically does not occur and that trough levels remained above the MIC for most organisms. There is limited data associating vancomycin peak concentrations with efficacy, however, adequate trough concentrations may better correlate with outcome. Data associating vancomycin concentrations with toxicity is also limited, and it remains unclear whether increased serum levels are the cause or the effect of decreased renal function. There may be some evidence that high troughs are associated with nephrotoxicity. The relationship between vancomycin concentrations and ototoxicity is even less clear. There is a trend toward monitoring trough levels ONLY in most patients based on this information. Adequate trough levels may be associated with efficacy (trough 1 to 2 times the MIC of the organism), and identifying a high trough may help avoid nephrotoxicity. If trough levels are in the therapeutic range, the chances of the peak being above 40 micrograms/milliliter is unlikely. Patients who may require both a peak and trough would include those receiving concomitant ototoxic or nephrotoxic drugs, patients with infections in the central nervous system, patients with endocarditis, or patients with infected hardware. Also included in this group would be patients with impaired or rapidly changing renal function (Wilhelm and Estes, 1999).

CONCLUSION

A wide variety of drugs are monitored via serum levels to optimize therapy, minimize toxicity, and aid therapeutic decisions. For many drugs the timing of the sample relative to the dosing schedule is critical. Clinical evaluation of the patient is always important in interpreting drug levels.

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REFERENCE: MICROMEDEX(R) Healthcare Series Vol. 111 expires 3/2002

DESIGNED BY HASHIM TAYEB (Bsc PHARM)