Steady-state pharmacokinetics of indinavir in cerebrospinal fluid and plasma among adults with human immunodeficiency virus type 1 infection.

Haas DW, Stone J, Clough LA, Johnson B, Spearman P, Harris VL, Nicotera J, Johnson RH, Raffanti S, Zhong L, Bergqwist P, Chamberlin S, Hoagland V, Ju WD
Clin Pharmacol Ther. 2000 68 (4): 367-74

PMID: 11061576 · DOI:10.1067/mcp.2000.109391

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 x 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.

MeSH Terms (12)

Acquired Immunodeficiency Syndrome Administration, Oral Adult Area Under Curve Blood-Brain Barrier Drug Administration Schedule HIV-1 HIV Protease Inhibitors Humans Indinavir RNA, Messenger RNA, Viral

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