Drug level monitoring, Plasma

Some indications for plasma level monitoring include inadequate response, relapse, serious or persistent adverse effects, use of higher than standard doses, suspected toxicity, elderly patients, children and adolescents, pregnant patients, patients of African or Asian descent (because of slower metabolism), cardiac disease, suspected noncompliance, suspected pharmacokinetic drug interactions, and changing brands. 

A microdialysis study was carried out to examine transport of oxycodone into the brain of rats [67], Oxycodone was administered by i.v. infusion, and unbound drug concentrations were monitored in both vena jugularis and striatum. Steady-state equilibrium was reached rapidly and drug levels in the two compartments declined in parallel at the end of the infusion. An unbound brain to unbound plasma ratio of 3.0 was measured which is 3- to 10-fold higher than for other opioids, and explains the similar in vivo potency of oxycodone in spite of lower receptor affinity. The authors interpret these data as de facto evidence of the existence of an as-yet unidentified transporter that carries oxycodone across the blood-brain barrier. 

Over the past 20 years there has been widespread interest in monitoring plasma antidepressant, particularly tricyclic, levels to optimize the response to treatment. One aspect of this research that is universally agreed upon concerns the extensive interindividual variability among patients, but it is still uncertain whether a knowledge of the plasma drug concentration is of clinical value. 

Carbamazepine, phenytoin, pheno-barbital, and other anticonvulsants (except for gabapentin) induce hepatic enzymes responsible for drug biotransformation. Combinations between anticonvulsants or with other drugs may result in clinically important interactions (plasma level monitoring ). 

Plasma level monitoring The majority of patients treated successfully had trough plasma levels between 0.2 and 1 mcg/mL. The probability of adverse experiences, especially cardiac, may increase with higher trough plasma levels, especially levels greater than 1 mcg/mL. Monitor trough plasma levels periodically, especially in patients with severe or moderate chronic renal failure or severe hepatic disease and CHF, as drug elimination may be slower. 

Morselli, P.L., Bianchetti, G., and Dugas, M. (1982) Haloperidol plasma level monitoring in neuropsychiatric patients. Ther Drug Monit 4 51-58. 

The use of drug plasma levels to effect optimal clinical response and to minimize adverse or toxic effects is standard practice in general medicine (e.g., phenytoin, digoxin), as well as in psychiatry (e.g., lithium, tricyclic antidepressants, valproate see Chapter 3). The theoretical basis for plasma level monitoring rests on several factors, including ... 

Aravagiri M, Ames D, Wirshing WC, et al. Plasma level monitoring of olanzapine in patients with schizophrenia determination by high-performance liquid chromatography with electrochemical detection. Ther Drug Monii 1997 19 307-313. 

The ability to monitor the presumed mechanism of action (i.e., monoamine oxidase inhibition) using platelets as a surrogate rather than monitoring the plasma drug level... 

Mycophenolate mofetil is available in both oral and intravenous forms. The oral form is rapidly metabolized to mycophenolic acid. Although the cytochrome P450 system is not involved, some drug interactions still occur. Plasma drug levels are frequently monitored, similar to the calcineurin inhibitors and PSIs. 

The Depakote form of valproic acid is approved for the acute phase of bipolar disorder. It is also commonly used on a long-term basis, although its prophylactic effects have not been as well established. Valproic acid is now frequently used as a first-line treatment for bipolar disorders, as well as in combination with lithium for patients refractory to lithium monotherapy and especially for patients with rapid cycling and mixed episodes. Oral loading can lead to rapid stabilization, and plasma levels must be monitored to keep drug levels within the therapeutic range. 

FIGURE 7—54. Heroic combo 10 SSRI plus NRI. Here, 5HT and NE are both single-boosted. The preferred NRI is selective reboxetine, as there are no drug interactions. Nonselective TCAs that are preferential NRIs such as desipramine, maprotilene, nortriptyline, or protriptyline can be combined if plasma drug levels of the TCA are monitored, especially if fluoxetine or paroxetine is the SSRI chosen. 

Like any diagnostic test, the measurement of drug plasma level is, however, justified only when the information provided is of potential therapeutic benefit and has been demonstrated in clinical trials. The clinical value of plasma level monitoring depends on how precisely the treatment outcome can be defined. On the other hand, when a precise therapeutic end point is difficult to define, monitoring of drug levels may be of considerable therapeutic assistance for clinicians [35],... 

Monitoring plasma and blood levels of the drug, if indicated, to ensure therapeutic levels and compliance with medication. Supporting the patient s compliance with treatment anticipat-... 

Serious drug interactions are uncommon with valproate. Approximately 25% of valproate metabolism is dependent on CYP isoenzymes. Valproic acid can cause severe liver damage during the first 6 months of treatment. Note interactions with aspirin and the need to monitor plasma free valproate levels. 

SSRIs-FLUOXETINE IMMUNOMODULATING DRUGS-CICLOSPORIN t plasma concentrations of cidosporin with risk of nephrotoxicity, myelosuppression and neurotoxicity Inhibition of CYP3A4-mediated metabolism of cidosporin these inhibitors vary in potency Monitor plasma cidosporin levels to prevent toxicity... 

LANREOTIDE ANTICANCER AND IMMUNOMODULATING DRUGS-CICLOSPORIN 1 plasma concentrations of cidosporin and risk of transplant rejection Lanreotide possibly induces CYP3A4-mediated metabolism of cidosporin Avoid co-administration if possible if not, monitor cidosporin levels closely... 

QUINUPRISTIN/ DALFOPRISTIN ANTICANCER AND IMMUNOMODULATING DRUGS -CICLOSPORIN t plasma concentrations of immunosuppressants, t risk of infections and toxic effects of cidosporin Due to inhibition of CYP3A4-mediated metabolism of cidosporin Monitor renal function prior to concurrent therapy, and blood count and cidosporin levels during therapy. Warn patients to report symptoms (fever, sore throat) immediately... 

GRISEOFULVIN ANTICANCER AND IMMUNOMODULATING DRUGS - CICLOSPORIN 1 plasma concentrations of ciclosporin (may be as much as 40%) and risk of rejection in patients who have received transplants Induction of ciclosporin metabolism Monitor ciclosporin levels closely... 

None for healthy individuals, although monitoring of plasma drug levels is potentially available at specialty laboratories for the expert... 

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