Steady-state pharmacokinetics of indinavir in cerebrospinal fluid and plasma among adults with human immunodeficiency virus type 1 infection.
Haas, David W. MD; Stone, Julie PhD; Clough, Lisa A. MD; Johnson, Benjamin MD; Spearman, Paul MD; Harris, Victoria L. EdD; Nicotera, Janet BA; Johnson, Regina H. BA; Raffanti, Stephen MD; Zhong, Ling PhD; Bergqwist, Paul BS; Chamberlin, Steven BS; Hoagland, Vicki MS; Ju, William D. MD
[Miscellaneous Article]
Clinical Pharmacology & Therapeutics.
68(4):367-374, October 2000.
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To characterize steady-state indinavir pharmacokinetics in cerebrospinal fluid and plasma, 8 adults infected with human immunodeficiency virus underwent intensive cerebrospinal fluid sampling while receiving indinavir (800 mg every 8 hours) plus nucleoside reverse transcriptase inhibitors. Nine and 11 serial cerebrospinal fluid and plasma samples, respectively, were obtained from each subject. Free indinavir accounted for 94.3% of the drug in cerebrospinal fluid and 41.7% in plasma. Mean values of cerebrospinal fluid peak concentration, concentration at 8 hours, and area under the concentration-time profile calculated over the interval 0 to 8 hours [AUC(0-8)] for free indinavir were 294 nmol/L, 122 nmol/L, and 1616 nmol/L [middle dot] h, respectively. The cerebrospinal fluid-to-plasma AUC(0-8) ratio for free indinavir was 14.7% /- 2.6% and did not correlate with indexes of blood-brain barrier integrity or intrathecal immune activation. Indinavir achieves levels in cerebrospinal fluid that should contribute to control of human immunodeficiency virus type 1 replication in this compartment. The cerebrospinal fluid-to-plasma AUC(0-8) ratio suggests clearance mechanisms in addition to passive diffusion across the blood-cerebrospinal fluid barrier, perhaps by P-glycoprotein-mediated efflux. (Clin Pharmacol Ther 2000;68:367-74.)
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