Peak and trough levels

Established standard dosage produces the target concentration (Ctarget) between normal peak and trough levels. 

FIGURE 3.7 Decline in serum gentamicin concentrations after therapy was stopped in a patient with nephrotoxicity ( ) and a patient who did not have this adverse reaction (o). Both patients had been treated with gentamicin at an S-hour dosing interval and had nearly identical elimination-phase half-lives and peak and trough levels. (Reproduced with permission from Colburn WA, Schentag JJr Jusko WJ, Gibaldi M. J Pharmacokinet Biopharm 1978 6 179-86.)... 

This would reduce fluctuation between peak and trough levels but would be awkward if only 0.5-g tablets were available. 

The concentration of medications that have a low TI (a narrow margin of safety) must be routinely monitored by assessing peak and trough levels of the plasma concentration of the medication by drawing blood samples from the patient. 

With dose escalation of combination oral products, be aware that the dose does not exceed recommended daily amounts for acetaminophen or ibuprofen. IV administration of codeine has been associated with allergic reactions related to histamine release. Parenteral administration of codeine is not recommended. Intermittent opioid administration is associated with wide fluctuation between peak and trough levels so that the patient may alternate between peak blood levels associated with untoward effects and trough levels associated with inadequate pain relief when treating severe pain. 

A 31-year-old woman was given intravenous rifampicin 300 mg every 8 hours and linezolid 600 mg every 12 hours for an MRSA infection. During rifampicin treatment her linezolid peak and trough levels were... 

Whether short-acting or sustained-release/extend-ed-duration preparations, or their combination, are most useful for step-3 analgesia is generally based on patient need. Patients who complain of occasional episodes of severe breakthrough pain are best treated with rapid-acting short-duration opioids, while those with constant discomfort or frequent episodes of pain appreciate the convenience and uniformity of relief provided by extended-duration opioids. The fact that extended-duration formulations produce steady-state concentration with fewer peak-and-trough levels may also reduce the incidence of annoying AEs such as nausea or somnolence. 

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