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Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.

ABSTRACT: HIV-1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross-sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV-1 RNA, and neopterin levels in subjects receiving either ritonavir-boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measured using rapid equilibrium dialysis and liquid chromatography/tandem mass spectrometry. Plasma and CSF HIV-1 RNA and neopterin were measured by Ampliprep/COBAS® Taqman® 2.0 assay (Roche) and enzyme-linked immunosorbent assay (ALPCO), respectively. CSF/plasma unbound drug concentration ratio was higher for ATV, 0.09 [95% confidence interval (CI) 0.06-0.12] than DRV, 0.04 (95%CI 0.03-0.06). Unbound CSF concentrations were lower than protein adjusted wild-type inhibitory concentration-50 (IC50 ) in all ATV and 1 DRV-treated subjects (P?

SUBMITTER: Delille CA

PROVIDER: S-EPMC4396178 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.

Delille Cecile A CA Pruett Sarah T ST Marconi Vincent C VC Lennox Jeffrey L JL Armstrong Wendy S WS Arrendale Richard F RF Sheth Anandi N AN Easley Kirk A KA Acosta Edward P EP Vunnava Aswani A Ofotokun Ighovwerha I

Journal of clinical pharmacology 20140408 9

HIV-1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross-sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV-1 RNA, and neopterin levels in subjects receiving either ritonavir-boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measure ...[more]

PMID: 24691856

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Project description:Cerebrospinal fluid (CSF) protein values decline over the first few months of life as the infant's blood-CSF barrier matures. However, published studies have not reported CSF protein reference values of Chinese infants and differ in the reported rate, timing, and magnitude of this decline. The objective of this study was to determine reference intervals for CSF protein using available data of children in southern China. This retrospective study included infants who had a lumbar puncture (LP) performed in the Department of Pediatrics of Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan of an urban tertiary care children's hospital between January 1, 2008 and May 31, 2018. Infants with conditions suspected or known to cause elevated CSF protein concentrations were excluded. Of 3712 infants undergoing LP, 1043 (28.1%) met inclusion criteria. Results showed that there is an age-related decline in CSF protein concentration. The median CSF protein value was 62 mg/dL [interquartile range (IQR): 47-81 mg/dL] in infants aged 0 to 56 days (group 1). The 95th percentile values were 116 mg/dL for infants 0 to 28 days and 80 mg/dL for infants 29 to 56 days. The 95th percentile values by age category were as follows: ages 0 to 14 days, 117 mg/dL; ages 15 to 28 days, 107 mg/dL; ages 29 to 42 days, 96 mg/dL; and ages 43 to 56 days, 74 mg/dL. The median CSF protein value was 21 mg/dL (IQR: 16-31 mg/dL) in infants aged 2 months to <3 years (group 2). The 95th percentile values were 57 mg/dL for infants 2 to <6 months and 34 mg/dL for infants 6 to ≤24 months. The 95th percentile values by age category were as follows: ages 2 to <3 months, 66 mg/dL; ages 3 to <4 months, 52 mg/dL; ages 4 to <5 months, 53 mg/dL; and ages 5 to <6 months, 42 mg/dL. We quantify the age-related decline in CSF protein concentrations among infants 2 years of age and younger and provide age-specific reference values. The values reported here can be used to interpret the results of LP in infants ≤2 years of age.

Dataset Information

Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.

Publications

Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.

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