Bilirubin as a surrogate marker for atazanavir in children

Polly Clayden, HIV i-Base

Findings for a study looking at paediatric atazanavir dosing and plasma bilirubin as a possible surrogate for atazanavir therapeutic drug monitoring (TDM) were presented at the 14th International Workshop on Clinical Pharmacology.

Although atazanavir dose is not predictive of Cmin, bilirubin might be a surrogate marker for atazanavir Cmin in this population.

TDM data of atazananvir from children and adolescents <18 years from a Canadian cohort were analysed. Atazanavir Cmin were estimated using a half-life of 10.10 and 5.58 hours with and without ritonavir boosting respectively, for levels taken more than 4 hours post-dose. Cmin below 0.15 was considered subtherapeutic. The investigators evaluated associations between dose Cmin and bilirubin Cmin.

Data from 15 participants and 35 TDMs were included in the analysis; the majority (93%) was black and 67% were girls. Their median age was 15 years (range 8-18), weight 49 kg (range 29-74) and body surface area 1.47 m2 (range 1.00 -1.88). The median atazanavir dose was 4.42 mg/kg (range 3.40 – 10.49) and 150 mg/m2 (range 125-299); most (74%) doses were boosted with ritonavir.

The median Cmin for TDMs for participants receiving unboosted atazanavir (n=5) was 0.05 mg/L (range 0-0.25); 60% of these were in the subtherapeutic range. For those receiving boosted atazanavir (n=19), median Cmin was 0.79 mg/L (range 0-1.85), 11% subtherapeutic. Cmin could not be evaluated in 11 TDMs.

The investigators found no association between Cmin and dose: mg/kg, p=0.81 and mg/m2, p=0.75; this remained similar after adjustment for ritonavir use. They found bilirubin concentrations of 18 ug/L to be predictive of Cmin > 0.15 mg/L with 95% sensitivity and 80% specificity, AUC 0.91 (95% CI 0.76 – 1.00). They noted that the results need to be confirmed in prospective studies.


Wong A et al. Biliruben as a surrogate marker for atazanavir concentrations in a pediatric population. 14th International Workshop on Clinical Pharmacology. 22-24 April 2013. Amsterdam. Poster abstract P_14.

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