Abstract
Objective: Protease inhibitors may not penetrate into the central nervous system in therapeutic concentrations, which may allow ongoing HIV replication and injury. The objective of this study was to determine atazanavir penetration into cerebrospinal fluid (CSF). Design: Single random plasma or paired plasma and CSF samples were drawn from participants enrolled in a multicenter, observational cohort study and taking atazanavir with or without ritonavir between October 2003 and October 2005. Methods: Plasma samples were assayed by high performance liquid chromatography and immunoassay; lower limit of detection was 45 ng/ml. CSF samples were assayed by immunoassay (ARK ATV-test); lower limit of detection was 5 ng/ml. Results: One hundred and seventeen participants (43 ± 7.7 years, 79% men, 81 ± 15 kg) had plasma or plasma and CSF paired samples drawn a median (interquartile range) of 10(5-17) h postdose. Median (interquartile range) plasma atazanavir concentrations with or without ritonavir were 1278 (525-2265) and 523 (283-1344) ng/ml. The median (interquartile range) CSF concentrations with or without ritonavir were 10.3 (<5-21.1) and 7.9 (6.6-22) ng/ml. Nineteen of 79 (24%) CSF samples were less than 5 ng/ml. CSF concentrations were less than 1% of plasma concentrations and near the atazanavir wild-type IC50 of 1-11 ng/ml. Conclusion: Atazanavir CSF concentrations are highly variable and 100-fold lower than plasma concentrations, even with ritonavir boosting. CSF concentrations of atazanavir do not consistently exceed the wild-type IC50 of atazanavir and may not protect against HIV replication in the CSF.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 83-87 |
| Number of pages | 5 |
| Journal | AIDS |
| Volume | 23 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2 2009 |
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Keywords
- Atazanavir
- Central nervous system
- Cerebrospinal fluid
- Pharmacology
- Protease inhibitors
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
Cite this
Low atazanavir concentrations in cerebrospinal fluid. / Best, Brookie M.; Letendre, Scott L.; Brigid, Eileen; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin; McArthur, Justin C.; McCutchan, J. Allen; Simpson, David M.; Ellis, Ronald; Capparelli, Edmund V.; Grant, Igor.
In: AIDS, Vol. 23, No. 1, 02.01.2009, p. 83-87.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Low atazanavir concentrations in cerebrospinal fluid
AU - Best, Brookie M.
AU - Letendre, Scott L.
AU - Brigid, Eileen
AU - Clifford, David B.
AU - Collier, Ann C.
AU - Gelman, Benjamin
AU - McArthur, Justin C.
AU - McCutchan, J. Allen
AU - Simpson, David M.
AU - Ellis, Ronald
AU - Capparelli, Edmund V.
AU - Grant, Igor
PY - 2009/1/2
Y1 - 2009/1/2
N2 - Objective: Protease inhibitors may not penetrate into the central nervous system in therapeutic concentrations, which may allow ongoing HIV replication and injury. The objective of this study was to determine atazanavir penetration into cerebrospinal fluid (CSF). Design: Single random plasma or paired plasma and CSF samples were drawn from participants enrolled in a multicenter, observational cohort study and taking atazanavir with or without ritonavir between October 2003 and October 2005. Methods: Plasma samples were assayed by high performance liquid chromatography and immunoassay; lower limit of detection was 45 ng/ml. CSF samples were assayed by immunoassay (ARK ATV-test); lower limit of detection was 5 ng/ml. Results: One hundred and seventeen participants (43 ± 7.7 years, 79% men, 81 ± 15 kg) had plasma or plasma and CSF paired samples drawn a median (interquartile range) of 10(5-17) h postdose. Median (interquartile range) plasma atazanavir concentrations with or without ritonavir were 1278 (525-2265) and 523 (283-1344) ng/ml. The median (interquartile range) CSF concentrations with or without ritonavir were 10.3 (<5-21.1) and 7.9 (6.6-22) ng/ml. Nineteen of 79 (24%) CSF samples were less than 5 ng/ml. CSF concentrations were less than 1% of plasma concentrations and near the atazanavir wild-type IC50 of 1-11 ng/ml. Conclusion: Atazanavir CSF concentrations are highly variable and 100-fold lower than plasma concentrations, even with ritonavir boosting. CSF concentrations of atazanavir do not consistently exceed the wild-type IC50 of atazanavir and may not protect against HIV replication in the CSF.
AB - Objective: Protease inhibitors may not penetrate into the central nervous system in therapeutic concentrations, which may allow ongoing HIV replication and injury. The objective of this study was to determine atazanavir penetration into cerebrospinal fluid (CSF). Design: Single random plasma or paired plasma and CSF samples were drawn from participants enrolled in a multicenter, observational cohort study and taking atazanavir with or without ritonavir between October 2003 and October 2005. Methods: Plasma samples were assayed by high performance liquid chromatography and immunoassay; lower limit of detection was 45 ng/ml. CSF samples were assayed by immunoassay (ARK ATV-test); lower limit of detection was 5 ng/ml. Results: One hundred and seventeen participants (43 ± 7.7 years, 79% men, 81 ± 15 kg) had plasma or plasma and CSF paired samples drawn a median (interquartile range) of 10(5-17) h postdose. Median (interquartile range) plasma atazanavir concentrations with or without ritonavir were 1278 (525-2265) and 523 (283-1344) ng/ml. The median (interquartile range) CSF concentrations with or without ritonavir were 10.3 (<5-21.1) and 7.9 (6.6-22) ng/ml. Nineteen of 79 (24%) CSF samples were less than 5 ng/ml. CSF concentrations were less than 1% of plasma concentrations and near the atazanavir wild-type IC50 of 1-11 ng/ml. Conclusion: Atazanavir CSF concentrations are highly variable and 100-fold lower than plasma concentrations, even with ritonavir boosting. CSF concentrations of atazanavir do not consistently exceed the wild-type IC50 of atazanavir and may not protect against HIV replication in the CSF.
KW - Atazanavir
KW - Central nervous system
KW - Cerebrospinal fluid
KW - Pharmacology
KW - Protease inhibitors
UR - http://www.scopus.com/inward/record.url?scp=58149141510&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149141510&partnerID=8YFLogxK
U2 - 10.1097/QAD.0b013e328317a702
DO - 10.1097/QAD.0b013e328317a702
M3 - Article
C2 - 19050389
AN - SCOPUS:58149141510
VL - 23
SP - 83
EP - 87
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 1
ER -