Therapeutic range

Fig. 1. Zero-order (controlled) deflvery versus first-order (immediate-release) deflvery (repeated adrninistration). In 2ero-order deflvery, the dmg is released at a constant rate within the therapeutic range. In first-order deflvery, each administration of the dmg (represented by J.) causes semm-dmg concentrations...

The narrow therapeutic range of digitalis related cardiotonic agents has resulted in an extensive effort to identify compounds in other structural classes which will improve cardiac function. The discovery of the heterocyclic cardiotonic drug, amrinone, led to research on other heterocyclic compounds for that indication. The imidazopyridine, isomazole (57), is representa-... 

Hirsh J, Dalen JE, Anderson DR et al (2001) Oral anticoagulants mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 119 (Suppl.) 8S-21S... 

Drug Interactions. Figure 1 Increase in drug concentration caused by pharmacokinetic interactions. Shadow represents the therapeutic range. 

Dtug interactions can cause serious problems in clinical practice especially when the affected dmg has the potential to be highly toxic. Furthermore, pharmacokinetic interactions are clinically important if the affected dmg has a narrow therapeutic range (i.e. small difference between the minimum effective concentration and the toxic concentration Fig. 1) and a steep concentration-response curve (i.e. significant alterations in pharmacological and/or adverse effects caused by small changes in blood concentration). 

Nurses must carefully monitor the patient s blood levels of drugs to ensure that they remain within the therapeutic range Any deviation should be reported to the primary health care provider. Because some dragp can cause toxic reactions even in recommended doses, the nurse should be aware of the signs and symptoms of toxicity of commonly prescribed drugs. 

The therapeutic range of theophylline blood levels is 10 to 20 p,g/mL. Levels greater than 20 pig/mL may cause toxicity. In some patients, toxicity may occur with levels between 15 and 20 pg/mL. Toxicity is more likely to occur in patients requiring high doses or during prolonged dierapy. 

Safety pharmacology studies may also be conducted in conjunction with the toxicity studies. These focus on identifying secondary pharmaceutical side effects that may occur, when the drug is administered in the therapeutic range. Emphasis is placed on identifying effects on vital systems, particularly the central nervous, cardiovascular and respiratory systems. 

The study will commence with the administration of low doses, as judged from the non-clinical data. As the study progresses - and provided that there are no indications that it is unsafe to do so - the dosage levels may be increased past the anticipated therapeutic range. Subjects are closely monitored for changes in vital signs (blood pressure, heart rate, body temperature, etc.) and the emergence of any adverse side effects (nausea, drowsiness, pain, headache, irritability, hair loss, etc.). 

It has been long believed that a lithium ion-selective electrode would render obsolete the flame photometer in the clinical laboratory. Lithium is administered to manic depressive psychiatric patients. Since the therapeutic range (0.5-1.5 mM) is quite close to the toxic range (>2 mM), it must be closely monitored. Most of the iono-phores propo d to date have not met the Li" /Na selectivity required for an interference-free assay. However, it has been reported that calibration in the presence of 140 mMNa permitted the analysis of Li in serum The errors observed are due to fluctuations in the Na concentrations in the sample. More selective ionophores would certainly improve the accuracy of this method. 

RESPONSE I left aside the hyperactivity issue because that is a literature study in itself It is also limited to adolescents, children, and juveniles, although there are some reports in adults as well. But there the therapeutic range for amphetamine is 20, 30, or 40 milligrams, and for methylphenidate it is slightly higher, which is actually the preferred agent. 

Resume lower dose when INR in therapeutic range... 

Overlap with parenteral therapy for a minimum of 4-5 d or until the INR has been in the therapeutic range for two consecutive days... 

Either UFH or LMWH should be administered to patients with NSTE ACS. Therapy should be continued for up to 48 hours or until the end of the angiography or PCI procedure. In patients initiating warfarin therapy, UFH or LMWHs should be continued until the International Normalized Ratio (INR) with warfarin is in the therapeutic range for 2 consecutive days. The addition of UFH to aspirin reduces the rate of death or MI in patients with NSTE ACS.47 Enoxaparin was mentioned as preferred over UFH in the 2002 ACC/AHA clinical practice guidelines, as two large clinical trials found a reduction in the combined endpoint of death, MI, or need for PCI in patients... 

If aPTT less than 2.5 times the control value, unfractionated heparin infusion should be started and adjusted to maintain aPTT in therapeutic range... 

Once seizure activity has ceased and the patient has stabilized, review the patient s therapeutic regimen. Evaluate and monitor the serum trough concentrations of AEDs with defined target ranges to determine patient-specific therapeutic ranges. If there is a known cause of SE, simplify the treatment regimen once the underlying cause has been treated. In patients... 

Continue to monitor AED serum trough concentrations approximately every 3 to 5 days until the AEDs have reached steady-state concentrations. Give additional loading doses or hold doses as needed to maintain trough concentrations in the patient s therapeutic range. Be sure to evaluate the time the sample was drawn to assure it is a trough level. 

Assess the AED serum concentration and adjust therapy as needed for agents with a defined therapeutic range (e.g., phenytoin, carbamazepine, valproic acid, and phenobarbital). Drug levels can also be used to determine adherence to medication regimens for agents that do not have defined ranges. 

The NSAIDs largely have supplanted colchicine as the treatment of choice, and many NSAIDs have been used successfully. These agents are most effective when given within the first 24 hours of the onset of pain. Most studies have shown similar results among agents, and all NSAIDs are considered to be effective. Doses at the higher end of the therapeutic range are often needed. 

Mild to moderate erythema has been noted with imiquimod use however, this generally suggests that the drug is reaching a therapeutic range and may be clearing the lesion.23... 

The clinical significance of this ethnic difference for psychiatry was found later. A study examining lithium tolerability found more side effects in African American patients with high RBC/plasma ratio even when the lithium levels were in the therapeutic range (Strickland etal., 1995). It is not known whether African Americans require lower doses and will respond with lower plasma levels. We do know that African Americans with mood disorders are less likely to be prescribed lithium either as primary treatment or adjunctive therapy (Valenstein etal., 2006 Kilbourne 8c Pincus, 2006). It is unknown as to whether the lack of tolerability at usual therapeutic doses is a factor. 

Transdermal controlled-release systems can be used to deliver drugs with short biological half-lives and can maintain plasma levels of very potent drugs within a narrow therapeutic range for prolonged periods. Should problems occur with the system or a change in the status of the patient require modification of therapy, the system is readily accessible and easily removed. 

Age-related variations in central nervous system (CNS) neurotransmitter production and receptor sensitivity are the most likely explanations for the pharmacodynamic differences observed between children and adults following administration of psychotropic medications [39a], Children have lower phenobarbital ratios than adults, and the ratio increases with gestational age [40,41]. Conversely, a lower therapeutic range for children has been identified for cyclosporine, phenytoin, and digoxin [42]. 

L. Z. Benet and J. E. Goyan, Bioequivalence and narrow therapeutic range drugs, Pharmacotherapy, 4, 433... 

---