TOPIC 10 Therapeutic drug monitoring
Introduction
1. To determine the drug is at therapeutic plasma concentrations: for most drugs, the easiest way to determine efficacy is by achieving a clinical endpoint. However for certain drugs, TDM is the only way to ensure the drug is working.
2. To determine if the drug is at toxic levels: some drugs have a ‘narrow therapeutic range’, where the difference between efficacious and toxic concentrations is small. TDM aids drug dosing, keeping plasma levels within the desired efficacious range and out of the toxic range.
Indication for TDM
• Possible drug interaction. The drugs mentioned are prone to multiple drug interactions in relation to enzyme induction and inhibition.
When to measure the drug level
• Trough level, i.e. sample immediately before the dose is due, when the drug concentration is at its lowest; or
Gentamicin
There are two methods of gentamicin dosing, the ‘conventional’ method and the ‘once-daily’ method (Table 10.1). ‘Once-daily’ is extremely dangerous if used in patients with renal dysfunction, for this reason, some units only use ‘conventional’ dosing.
Table 10.1 Gentamicin dosing regimens
| Conventional dosing | 1–1.5 mg/kg IV with frequency depending on estimated creatinine clearance (CrCl). If CrCl: |
| Indication | Avoid toxicity (trough) and efficacy (peak) |
| How it is done | Take a peak and trough level before the third dose or on day 2 |
| Target | The trough level should be <2 mg/mL. The peak should be 4–8 mg/mL |
| Interpretation | |
| Once-daily dosing | |
| Contraindication | Once-daily dosing is not appropriate for a CrCl <20 mL/minute, oliguria, haemofiltration, endocarditis, severe liver disease, cystic fibrosis, major burns, prophylaxis or infants <6 months |
| Indication | For safe and effective therapy |
| How it is done | Levels any time between 6 and 14 hours postdose |
| Interpretation |
For obese patients, use corrected body weight:
