Boosted saquinavir PK in once-daily regimes

Simon Collins, HIV i-Base

Marta Boffito and colleagues from Liverpool University investigated steady-state PK of two once-daily boosted saquinavir regimes. Doses studied were 1600mg and 2000mg saquinavir, each boosted by 100mg ritonavir and drug levels were compared to those achieved in the same 18 HIV-positive patients on their original 1000mg/100mg twice daily regimes.

The interest in these possibilities is heightened by a new 500mg formulation of saquinavir that will considerably reduce the pill count.

Saquinavir was given with a 40g-fat meal on day one, then switched to 1600/100mg on day two and switched again on day 12 to 2000/100mg. Intensive PK was measured by HPMC on days 0, 11 and 22.

A summary of PK results are shown below in Table 1 but were skewed by one patient who had a Ctrough of over 3000ng/mL in 2000/100 mg arm. When this patient was excluded from the analysis the trough levels were reduced by 59% in the 2000/100mg once-daily arm compared to 1000/100mg twice-daily. Saquinavir AUC, Cmax and T1/2 increased by 30%, 136% and 29% respectively when excluding the outlier.

Although this is a small data set, trough levels at the 1600/100mg and 2000/100mg doses are clearly reduced compared to twice-daily dosing. Only one patient in each of the once-daily arms had a saquinavir Ctrough below the minimum effective concentration (MEC) target of 50ng/mL for treatment naïve patients.

The authors conclude that the higher drug exposure was driven by higher levels of absorption without evidence of increased toxicity (ALT, AST, glucose, TC and TG) in the short-term. Clearly longer follow-up is required in larger studies before this could be routinely recommended.

Table 1: PK parameters in eight HIV-positive patients

Dose: saquinavir/ritonavir; Median (IQR)
Parameter 1000/100 BID 1600/100 QD 2000/100 QD
Ctrough (ng/mL) 569 95 209
Range 138-2226 20-635 31-3128
(250, 1178) (57, 192) (100, 529)
Cmax (ng/mL) 2152 2835 4241
(1268, 3321) (1730, 2631) (3023, 5902)
AUC0-24hr(ng.h/mL) 28733 17877 31418
(14083, 46076) (1095, 34166) (22705, 55292)
t1/2 (hr) 3.31 4.62 4.47
(2.96, 4.90) (4.09, 4.93) (4.21, 5.43)


Boffito M, Dickinson L, Hill A et al. Saquinavir/ritonavir (SQV/r) pharmacokinetics (PKs) in HIV+ subjects: 1000/100mg BD vs 1600/100 and 2000/100mg once daily (OD). 43rd ICAAC, September, 2003; Abstract A-1612.

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