Therapeutic drug monitoring of efavirenz: trough levels cannot be estimated on the basis of earlier plasma determinations.
OBJECTIVE
The few studies evaluating the relation between efavirenz (EFV) plasma levels and efficacy have only shown a weak association. They are based on population pharmacokinetics and/or estimation of trough levels from samples obtained at different time points, because this drug is usually taken at bedtime. We explore whether a limited sampling strategy could provide a good estimation of EFV trough levels and area under the curve (AUC).


METHODS
Fifty-nine 24-hour profiles from patients on 600 mg of EFV administered once daily were included for the analysis. Plasma drug concentrations were determined by a validated high-performance liquid chromatography assay. The relation between EFV plasma concentrations at C8, C12, and C16 and the corresponding C24 and AUC0-24 values were assessed in different index sets, and their predictive performances were evaluated in the validation sets.


RESULTS
EFV plasma levels at C12 and C16 are precise predictors of AUC0-24 (<or=10% mean relative prediction errors). The estimation of C24 levels from EFV plasma concentrations at C8, C12, or C16 is not precise enough (18%-62% mean relative prediction errors), however, and the use of C12 and C16 in combination does not improve the accuracy of C24 prediction.


CONCLUSIONS
No adequate substitute for collecting blood 24 hours after dosing emerged from this analysis, which might explain the weak association observed between EFV plasma levels and treatment outcomes in the studies available.
López-Cortés
Luis F
LF
Infectious Diseases Service, Hospitales Universitarios Virgen del Rocío, Seville, Spain. lflopez@telefonica.net
Ruiz-Valderas
Rosa
R
Marín-Niebla
Ana
A
Pascual-Carrasco
Rosario
R
Rodríguez-Díez
Magdalena
M
Lucero-Muñoz
María J
MJ
D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D048588:Benzoxazines; D003521:Cyclopropanes; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz