Pharmacokinetics of atazanavir/ritonavir plus raltegravir

1 June 2012. Related: Conference reports, Antiretrovirals, PK and drug interactions, PK Workshop 13th 2012.

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Current dosing for raltegravir is 400 mg twice daily, but atazanavir increases raltegravir exposure by 40-72% probably through UGT1A1 inhibition.

This pharmacological pilot phase II study investigated the pharmacokinetics of raltegravir 400 mg once daily in 6 HIV positive men receiving 2 NRTIs plus atazanavir/r. Three patients were taking tenfovir/FTC.

Half-dose raltegravir exposure, when combined with atazanavir/r, seemed to be adequate in the majority of patients, with only one trough value below the IC95 (15 ng/ml). Raltegravir AUC, Cmax and Ctrough (median, IQR) were 14497 ng.h/ml (13845-28325), 3984 ng/ml (3863-6703) and 40 ng/mL (22-51), respectively. Median (IQR) atazanavir AUC, Cmax, and Ctrough were 26414 ng.h/mL (23037-33109), 2284 ng/mL (1706-2666) and 526 ng/mL (397-604), respectively. Median (IQR) ritonavir AUC, Cmax and Ctrough were 9147 ng.h/mL (8052-12860), 1107 ng/mL (983-1244), 99 ng/mL (61-183), respectively.

The AUC of raltegravir 400 mg once daily in this study was similar to the AUC of the 800 mg once daily dosage in the QDMARK study (14895 ng.h/ml), and resulted in two-fold higher than the reported AUC values with standard 400 mg twice-daily dosage (6340 to6910 ng.h/ml). However, QDMARK reported that raltegravir 400 mg once-daily with atazanavir/r resulted in poorer rates of viral suppression.

Atazanavir concentrations were comparable to historical data and Ctroughs were above the target level (150 ng/mL) in all patients.

Reference:

Calcagno A et al.Pharmacokinetics of raltegravir 400 mg once-daily in combination with atazanavir/ritonavir plus two NRTIs. 13th PK Workshop, 16-18 April 2012, Barcelona. Poster abstract P_05.