OIV-A-2Gender-specific differences in the pharmacokinetics of ritonavir (RTV)-boosted saquinavir (SQV) in men, women and pregnant women

Abstract

BACKGROUND SQV/RTV 1000/100mg BID plus nucleos(t)ide reverse transcriptase inhibitors (NRTI) is a frequently used HIV-therapy during pregnancy. However not much is known about the steady-state pharmacokinetics (PK) of SQV in late pregnancy. OBJECTIVE To evaluate the plasma exposure of SQV/RTV 1000/100mg BID and possible influencing factors in pregnant women (n=14), women (n=12) and men (n=66). METHODS Patients performed a standardized 12h-PK assessment at steady state. SQV/RTV concentrations were measured by LC/MS/MS. The influence of ethnicity, gender, age, bodyweight and co-medication on Cmin, Cmax; AUCss, CLtot, t1/2 and volume of distribution was analysed in a multiple linear regression analysis by the stepwise deletion of variables. RESULTS Mean(±SD) SQV Cmin, Cmax and AUCss were 524(±425)ng/mL, 2639(±1406)ng/mL and 18015(±10761)ng*h/mL for men, 966(±574)ng/mL, 3653(±2291)ng/mL and 26477(±14991)ng*h/mL for women and 639(±300)ng/mL, 2629(±1350)ng/mL and 18448(±9152)ng*h/mL for pregnant women. The differences between men and women reached statistical significance (Cmin, p=.002; Cmax, p=.043; AUCss, p=.021) The multivariate analysis identified bodyweight (p=.003) and body-mass index (p=.006) as factors influencing the SQV plasma exposure. CONCLUSIONS Non pregnant women exhibited higher SQV plasma levels than men and women in late stage of pregnancy. SQV exposure depends on bodyweight and shows a great variability. TDM should therefore be performed frequently. Clinical Pharmacology & Therapeutics (2005) 79, P57–P57; doi: 10.1016/j.clpt.2005.12.115