Gastrointestinal dysfunction may affect absorption and consequently therapeutic benefit from drugs such as Saquinavir (SQV), a protease inhibitor. A study was designed to determine pharmacokinetics (PK) parameters of SQV in AIDS patients with various gastrointestinal alterations.Methods: SQV was administered as a single 600 mg oral dose with a light breakfast including grapefruit juice in an open label PK study in HIV patients. The study evaluated the influence of intestinal permeability on SQV PK in 30 HIV patients with severe diarrhea or wasting syndrome. Only three plasma samples were collected in a randomized manner from each patient following administration of SQV according to population PK analyse. Intestinal permeability was assessed using D-xylose, mannitol and lactulose. A five hour urine collection was made and analysis of sugar probes was done by performance liquid chromatography.Results: Preliminary data are presented for 15 (CDC 3) out of 30 planned patients including 13 men and 2 women, mean weight: 54.8±10.7 kg. Eight patients were receiving a concommitant antiretroviral therapy. Of the 15 patients, 10 had severe diarrhea cryptosporidia (2), microsporidia (1), cryptosporidia + microsporidia (3) and CMV-associated digestive disease (2). Five patients had wasting syndrome. Plasma concentrations of SQV were between 30 and 100 ng/mL in 5 patients and above 100 ng/mL in 10 patients. All patients had greater changes in intestinal permeability.Conclusions: The decreased absorption of mannitol argues that the functional absorptive surface of the intestine decreases as HIV diseases progresses. Plasma concentrations of SQV administered to HIV patients with severe diarrhea or wasting syndrome are at least equal to those achieved in healthy volunteers.