Trough concentration/levels

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. 

Dipyridamole Peak plasma levels of dipyridamole are achieved approximately 2 hours after administration of a daily dose of 400 mg dipyridamole and aspirin combination (given as 200 mg twice daily). The peak plasma concentration at steady-state is approximately 1.98 mcg/mL and the steady-state trough concentration is approximately 0.53 mcg/mL. 

Monitoring Perform auditory function serial tests and monitor serum levels. When monitoring vancomycin serum levels, draw a peak concentration 1.5 to 2.5 hours after the completion of a 1-hour infusion and a trough concentration within 1 hour of the next scheduled dose. Peak levels are generally expected to be in the 30 to 40 mg/mL range and trough levels in the 10 to 15 mg/mL range. 

Herceptin with cisplatin, doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel. A comparison of serum levels of trastuzumab given in combination with various chemotherapeutic agents did not suggest the possibility of any pharmacokinetic interactions except in combination with paclitaxel. Although not statistically signihcant, mean serum trough concentrations of trastuzumab were consistently elevated, about 1.5-fold, when Herceptin was administered in combination with paclitaxel. However, trastuzumab and paclitaxel were used concurrently in clinical trials with positive outcome results. The concurrent administration of anthracyclines, cyclophosphamide, and trastuzumab increased the incidence and severity of cardiac dysfunction during clinical trials. 

Until cyclosporine blood trough concentrations reach preconversion levels, monitoring should be undertaken every 4 to 7 days... 

Tacrolimus can be administered orally or intravenously. After oral administration, peak concentrations are reached after 1-4 hours. The half-life of the intravenous form is approximately 9-12 hours. Like cyclosporine, tacrolimus is metabolized primarily by P450 enzymes in the liver, and there is a potential for drug interactions. The dosage is determined by trough blood level at steady state. Its toxic effects are similar to those of cyclosporine and include nephrotoxicity, neurotoxicity, hyperglycemia, hypertension, hyperkalemia, and gastrointestinal complaints. 

In the study of Wang et al dasatinib trough levels appear to correlate strongly with toxicity but not with efficacy. The lowest trough concentration was achieved with the lowest dose regimen (100 mg once daily) which has been shown to have the optimal therapeutic index among the regimens tested [74],... 

In these phase I studies, trastuzumab displayed dose-dependent pharmacokinetics, with a serum half-life ranging from 1 day at the 10-mg dose level to 14 days at the 500-mg dose level. Importantly, when administered at the higher dose levels, consistent serum trough concentrations of trastuzumab above 10 pg/ml were achieved, which was the target concentration based on the in vitro antiproliferative activity. Soluble HER ECD was detected in 24 of 28 patients and was correlated with altered trastuzumab pharmacokinetics. Also, in contrast to 4D5 therapy, no human antihuman antibodies (HAHA) were observed following trastuzumab administration. 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

FIGURE 2.7 Plasma concentrations after repeated administration of the same drug dose to tw o hypothetical patients whose elimination clearance is the same but whose distribution volumes differ. The patients have the same Css but the larger distribution volume results in lower peak and higher trough plasma levels (solid line) than when the distribution volume is smaller (dashed line). 

With chronic use the plasma t) of lithium is 15-30 h. Lithium is usually given 12-hourly to avoid unnecessary fluctuation (peak and trough concentrations) and maintain a plasma concentration just below the toxic level. A steady-state plasma concentration will be attained after about 5-6 days (i.e. 5 x t) ) in patients with normal renal... 

The time to collect the specimen is determined by the reason for monitoring. If a patient displays any symptoms of intoxication, then the peak blood concentration is of interest. This specimen is collected 4 to 5 hours after the dose, although the peak level may be delayed up to 8 hours if the drug is given in conjunction with food or drugs that increase stomach acidity. If the principal question at hand is adequate therapy, then the trough concentration is more useful that specimen is collected just before the next dose is given. 

Recommended baseline and routine laboratory tests for valproate are listed in Table 68-12. Data from clinical trials in acutely manic patients indicated that there was an earlier response when trough serum levels were greater than 45 mcg/mL during the Hrst week of treatment. Although therapeutic serum concentrations of valproic acid have not been established in bipolar disorder, most clinicians use the anticonvulsant therapeutic range of 50 to 125 mcg/mL taken 12 hours after the last dose. Patients with cyclothymia or mild bipolar II disorder may have a therapeutic response to lower doses and blood levels, whereas some patients with a more severe form of bipolar disorder may require up to 150 mcg/mL. Serum valproic acid levels are usually determined every 1 to 2 weeks during the first 2 months, and then every 3 to 6 months during maintenance therapy. ... 

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