Efficacy of a new oral lubricant solution in the management of psychotropic drug-induced xerostomia: a randomized controlled trial.

Objective: Xerostomia is a subjective sensation of mouth dryness often occurring as an unwanted effect of psychotropic drugs.

Methods: The clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray (1 or 2 sprays up to 4 times daily) in the treatment of xerostomia was compared with those of a commercially available artificial saliva substitute (ASS [Saliveze]) in a 2-week, open-labeled, randomized, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness by means of a 10-cm-long visual analog scale, objective blinded assessment of the oral tissue condition by a dental hygienist by means of a 4-point ordinal scale, and subjective patient-based assessment of dry mouth symptoms by means of dichotomous responses to a questionnaire.

Variation in oral clearance of saquinavir is predicted by CYP3A5*1 genotype but not by enterocyte content of cytochrome P450 3A5.

Objective: Saquinavir, a widely prescribed human immunodeficiency virus 1 protease inhibitor, has a low and variable oral bioavailability that has been attributed to extensive first-pass extraction mediated by hepatic or intestinal cytochrome P450 (CYP) 3A4 and intestinal P-glycoprotein (P-gp). The polymorphic CYP3A5 has also been shown to influence the saquinavir metabolite/parent urinary ratio, suggesting a role for CYP3A5.

Methods: Twenty healthy subjects received a single oral dose of saquinavir (600 mg) with water (control) and, on a separate occasion, with Seville orange juice (a selective intestinal CYP3A4/5 inhibitor).

Contributions of CYP3A4, P-glycoprotein, and serum protein binding to the intestinal first-pass extraction of saquinavir.

Using CYP3A4-expressing Caco-2 cell monolayers, we assessed the roles of CYP3A4-mediated metabolism, P-glycoprotein (P-gp)-mediated efflux, and serum protein binding in determining the extent of the intestinal first-pass extraction (E(i)) of saquinavir. Saquinavir (5-40 microM) was added to the apical compartment of culture inserts. After 3 h, apical and basolateral media and cell scrapings were analyzed for saquinavir and a major CYP3A4-mediated metabolite (M7).