Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 52
Why was the second concentration so high?
ОглавлениеThe predicted concentration on her increased dose can be calculated as before, i.e.
In this case, the measured concentration was reasonably consistent with the predicted value and her actual Vmax can therefore be estimated from the measured concentration, i.e.
Using her actual Vmax and a Km of 4.4 mg/L, average steady‐state concentrations can be predicted for various doses (Table 1.6). Note that a small change in the dose produces a disproportionately large increase in concentration, especially at higher concentrations.
Table 1.6 Predicted steady‐state phenytoin concentrations for clinical scenario.
| Dose (mg/day) | Steady‐state concentration | |
|---|---|---|
| (mg/L) | (μmol/L) | |
| 225 | 6 | 24 |
| 250 | 7 | 28 |
| 275 | 9 | 36 |
| 300 | 13 | 52 |
| 325 | 18 | 72 |
| 350 | 28 | 112 |
| 375 | 55 | 220 |
It is known that a concentration of 6 mg/L does not control her seizures and she experiences toxicity with 28 mg/L. Her ideal dose is therefore likely to lie in the range 275–325 mg/day. It would be sensible to start with 300 mg/day and adjust the dose (if necessary) according to her response. It would also be useful to emphasise to the patient that she must comply with her prescribed dose in order to obtain the maximum benefit from her therapy.
Comment. This case illustrates the non‐linearity of phenytoin dose–concentration relationships and the difficulty of interpreting phenytoin concentrations when dosage history is uncertain (as frequently occurs with outpatients). It also demonstrates the value of using serial measurements (the two results were clearly inconsistent with each other) and average dose requirements to assess adherence.
