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Following administration of the 10th dose, blood was collected serially over 8\u2003h for measurement of saquinavir plasma concentrations. Saquinavir pharmacokinetic parameter values were determined using noncompartmental methods and compared between males and females. CYP3A phenotype (using oral midazolam) and MDR\u20101 genotypes at positions 3435 and 2677 were determined for all subjects in order to characterize possible mechanisms for any observed sex\u2010related differences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was no significant difference in saquinavir AUC<jats:sub>0\u22128<\/jats:sub>or any other pharmacokinetic parameter value between the sexes. These findings persisted after mathematically correcting for total body weight. The mean weight\u2010normalized AUC<jats:sub>0\u22128<\/jats:sub>was 29.9 (95% confidence interval 15.5, 44.3) and 29.8 (18.6, 40.9)\u2003ng\u2003h<jats:sup>\u22121<\/jats:sup>\u2003ml<jats:sup>\u22121<\/jats:sup>\u2003kg<jats:sup>\u22121<\/jats:sup>for males and females, respectively. No significant difference in CYP3A phenotype was observed between the groups; likewise, the distribution of MDR\u20101 genotypes was similar for males and females.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In contrast to previous study findings, results from this investigation showed no difference in saquinavir pharmacokinetics between males and females. The discrepancy between our findings and those previously reported may be explained by the fact that we evaluated HIV\u2010seronegative volunteers and administered saquinavir in the absence of concomitant protease inhibitors such as ritonavir. Caution must be exercised when extrapolating pharmacokinetic data from healthy volunteer studies (including sex\u2010based pharmacokinetic differences) to HIV\u2010infected populations or to patients receiving additional concurrent medications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2006.02593.x","type":"journal-article","created":{"date-parts":[[2006,2,14]],"date-time":"2006-02-14T10:07:24Z","timestamp":1139911644000},"page":"379-388","source":"Crossref","is-referenced-by-count":3,"title":["Lack of sex\u2010related differences in saquinavir pharmacokinetics in an HIV\u2010seronegative cohort"],"prefix":"10.1111","volume":"61","author":[{"given":"Sarah M.","family":"Robertson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Formentini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul M.","family":"Alfaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ven","family":"Natarajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Falloon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott R.","family":"Penzak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,2,14]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121453"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(98)90146-1"},{"key":"e_1_2_5_4_2","first-page":"2159","article-title":"Are cytochrome P45 3A enzymes in the small intestine responsible for different cyclosporine metabolite patterns in stable male and female renal allograft recipients after co\u2010administration of diltiazem?","volume":"28","author":"Christians U","year":"1996","journal-title":"Transplant Proc"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/00912700022008883"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.128388"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241050-00002"},{"key":"e_1_2_5_8_2","first-page":"1011","article-title":"Interindividual variation of expression of P\u2010glycoprotein in normal human liver and secondary hepatic neoplasms","volume":"275","author":"Schuetz EG","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_9_2","unstructured":"Fortovase\u00ae(saquinavir soft gelatin capsules) package insert. 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