This study is being done to find out how much of the drug raltegravir (RGV) gets into
cerebrospinal fluid (CSF), compared to how much get into the blood and to find out if normal
changes in a certain gene in your body affects how much RGV gets into the CSF.
The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in the blood-brain
barrier where it limits entry of substrate drugs into the central nervous system.
Raltegravir (MK-0158), a new HIV-1 integrase inhibitor and potentially major addition to the
therapeutic armamentarium against HIV, is a substrate for P-gp. Studies are warranted to
elucidate the relevance of P-gp transport for raltegravir in the central nervous system.
1. Able to give informed consent.
2. Negative HIV-1 serology.
3. At least 18 but no more than 55 years of age.
4. Body mass index <30.
5. Estimated creatinine clearance ≥ 50 mL/minute within 30 days prior to study entry.
6. Within 30 days prior to study entry:
- Absolute neutrophil count ≥ 1,000/mm3.
- Hemoglobin ≥ 12.5 g/dL for males and ≥ 11.5 g/dL for females.
- Platelet count ≥ 100,000/mm3.
- AST, ALT, and total bilirubin within normal range.
- Alkaline phosphatase < or = 1.5 x upper limit of normal.
7. Female study volunteers of reproductive potential must have a negative serum or urine
pregnancy test performed within 30 days before study entry.
8. Must agree not to participate in a conception process.
9. Drug transporter gene ABCB1 position 3435 genotype C/C or T/T.
1. Use of any medication that is metabolized by CYP3A or UGT1A1.
2. Anticipated need to take any medication that is metabolized by CYP3A or UGT1A1 during
3. Active drug use or dependence.
4. Inability to abstain from alcohol-containing beverages, grapefruit, and grapefruit
5. Serious illness that would interfere with study participation.
6. Hospitalization for any reason or therapy for serious illness within 14 days prior to
7. History of hypersensitivity to study drug or its formulation.
8. As determined by the investigator, a significant active or previous history of
cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric,
endocrine, or immunologic disease(s). This is inclusive of chronic illnesses such as
hypertension, coronary artery disease, arthritis, diabetes, any chronic
gastrointestinal conditions that may affect drug absorption, etc.
10. Evidence of CNS infection or space occupying lesion by history or physical
11. History of significant CNS disorder.
12. Prisoners or subjects who are compulsorily detained.
13. ABCB1 position 3435 C/T heterozygosity.