title: No significant influence of saquinavir hard-gel capsule administration on pharmacokinetics of lopinavir in combination with ritonavir: a population approach.
abstract: The influence of saquinavir hard-gel capsules on lopinavir pharmacokinetic parameters was investigated using a population approach. Forty-nine patients infected with human immunodeficiency virus type 1 and treated with lopinavir/ritonavir, nucleoside/nucleotide reverse transcriptase inhibitors plus saquinavir (group A), and 118 patients treated with lopinavir/ritonavir plus nucleoside/nucleotide reverse transcriptase inhibitors (group B) were included in the study. No significant relationship was established between the presence or the daily dosage of saquinavir in the treatment and lopinavir population pharmacokinetic parameters. The values (mean+/-standard deviation) of the individual apparent clearance (5.0+/-1.8 vs. 5.0+/-3.2 L/h), volume of distribution (66.6+/-1.6 vs. 66.8+/-1.9 L), absorption rate constant (0.37+/-0.01 vs. 0.37+/-0.03 hours), and trough plasma concentration (5.5+/-2.3 vs. 5.3+/-1.9 mg/L) of lopinavir are not significantly different between groups A and B. This lack of influence of saquinavir on lopinavir pharmacokinetics makes the use of this combination in salvage therapy easier.
authors.affiliation: Clinical Pharmacology Department, Hôtel Dieu, Nantes, France. eric.dailly@chu-nantes.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolliet
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001499:Bayes Theorem; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D005260:Female; D005782:Gels; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir; D008297:Male; D008657:Metabolic Clearance Rate; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D012044:Regression Analysis; D012189:Retrospective Studies; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019258:Saquinavir / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D002214:Capsules; D005782:Gels; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019258:Saquinavir; D019438:Ritonavir