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Efavirenz
Plasma Levels Can Predict Treatment Failure and Central Nervous
System Side Effects in HIV-1-Infected Patients [Marzolini C,
et al. AIDS 2001;15:71]: The
authors measured plasma efavirenz levels in 130 recipients of the
drug at an average of 14 hours after drug intake. Concentrations
ranged from 125 to 15,230 ug/l. Virologic failure was noted in 50%
of patients with levels <1000 ug/l, and CNS toxicity was approximately
three times greater in those with levels >4000 ug/l. The authors
conclude that there are substantial variations in plasma levels
of efavirenz and that therapeutic drug monitoring may be important
for optimal treatment.
Comment: Therapeutic monitoring seems to be getting more
attention, but almost all of the emphasis is on PI therapy, especially
indinavir, due to the relatively close toxic-therapeutic ratio with
this drug. Efavirenz levels are generally high relative to EC50
concentrations for wild-type HIV; the plasma half-life is long (40
- 55 hours) so that the "pharmacologic barrier" is one
of its best advantages. This report consequently comes as a surprise.
It is quite possible that some of the variation could be ascribed
to non-adherence and to drug interactions; these issues were not
discussed in any detail.
posted
3/13/2001
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