Gender and pharmacokinetics of saquinavir

Polly Clayden, HIV i-Base

Laura Dickenson from Liverpool University presented findings from an evaluation of the impact of gender on saquinavir hard gel/ritonavir pharmacokinetics in HIV positive patients and found significant differences. In a separate study this group examined P-glycoprotein and MRP expression in PBMCs in an attempt to find a mechanism [1].

In a retrospective analysis of a group of 34 patients (6 women) the investigators reported a higher median saquinavir AUC12h (13804 vs 2477ng.h/ml, p=0.05), Cmax (2343 vs 4373ng/ml p=0.05) and Cmin (271 vs 786ng/ml, p=0.05) in women vs men. They also reported a highly significant median ritonavir AUC12h (7587 vs 15412ng.h/ml, p<0.0001), Cmax (1052 vs 2818ng/ml p<0.001) and Cmin (192 vs 558ng/ml, p<0.001) in women vs men. They noted that saquinavir and ritonavir half life was similar between genders (p=55 and 0.36 respectively).

Drug transporter expression was evaluated in PBMCs isolated from 93 patients (30 women). Median p-glycoprotein expression was 0.66RFU in women compared to 0.89RFU in men (p=0.0016). Median expression of MRP in women was 0.14RFU compared to 0.35RFU in men (p=0.018).

Dr Dickenson explained that these findings were in agreement with previous studies but the clinical impact is unclear, although she did note that in ACTG 359 women using protease inhibitors in salvage therapy were more likely to have a viral load of <500 copies/ml than men [2]

However, a study from Robertson and colleagues evaluating pharmacokinetic values for soft gel saquinavir in a group of HIV-negative volunteers reported no significant differences between genders receiving the drug as a single PI [3]. The authors suggested that HIV serostatus and the presence of another PI may contribute to gender based differences in saquinavir pharmacokinetics.


  1. Dickinson L, Back D, Chander B, et al. The impact of gender on saquinavir hard-gel/ritonavir (1000/100 mg bid) pharmacokinetics and PBMC transporter expression in HIV-1 infected individuals. 6th International Workshop on Clinical Pharmacology of HIV Therapy. 28-30 April 2005. Quebec. Abstract 9.
  2. JID 189:1176, 2004
  3. Robertson S, Fallooon J, Formentini E et al. Lack of sex-related differences in saquinavir pharmacokinetics in an HIV seronegative cohort. 6th International Workshop on Clinical Pharmacology of HIV Therapy. 28-30 April 2005. Quebec. Abstract 50.

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