| |
Effect of Simultaneous or Staggered Dosing of Saquinavir (SQV), Ritonavir (RTV), and Nelfinavir (NFV) on Pharmacokinetic (PK) Interactions T. BLASCHKE*1, C. FLEXNER2, L. SHEINER3, and S. ROSENKRANZ4.
1Stanford Univ., CA; 2Johns Hopkins Univ., Baltimore, MD; 3Univ. of California, San Francisco; and 4SDAC/Harvard Sch. of Publ. Hlth., Boston, MA
Objective: To determine whether local drug interactions mediated
by CYP 3A or P-glycoprotein in the intestinal mucosa affect the pharmacokinetics
of dual protease inhibitor (PI) combinations.
Methods: 18 healthy volunteers participated in a 6-period study;
each period they ingested single doses of two Pls either simultaneously
or separated by 4 h. The order of the periods was balanced, and they were
separated by at least 2 d. Multiple samples for PK were obtained for 24
h after dosing, and concentrations were determined by HPLC. The area under
the concentration-time curve (AUC) was calculated for each drug by noncompartmental
methods.
Results: The table shows the AUC for simultaneous dosing, and the
ratio of staggered/simultaneous dosing AUCs (# denotes ratio value 
Conclusions: The AUC of SQV is smaller when given before the metabolic
inhibitors RTV and NFV. RTV increases SQV and NFV AUCs; the effect lasts
beyond the time that RTV can be measured in plasma. NFV and RTV AUCs
were not influenced by simultaneous vs staggered dosing.
Key Words: dosing schedule, drug interactions, intestinal transport
|
