Zidovudine and lamivudine reach higher concentrations in ventricular than in lumbar human cerebrospinal fluid
| Autor: | Christian Eggers, Richard M. W. Hoetelmans, Stephanie Läer |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Efavirenz AIDS Dementia Complex Anti-HIV Agents Immunology HIV Infections Gastroenterology Spinal Puncture 03 medical and health sciences chemistry.chemical_compound Zidovudine 0302 clinical medicine Cerebrospinal fluid Indinavir Internal medicine medicine Immunology and Allergy Humans 030212 general & internal medicine business.industry Stavudine Lamivudine Viral Load 030104 developmental biology Infectious Diseases chemistry HIV-1 RNA Viral Ritonavir Drug Therapy Combination business Saquinavir medicine.drug |
| Zdroj: | AIDS (London, England). 34(13) |
| ISSN: | 1473-5571 |
| Popis: | Objective For the treatment of HIV-1-related brain disease and for the prevention of the brain becoming a viral reservoir, it is important that antiretroviral agents reach sufficient concentrations in the CNS. To date, human brain pharmacokinetic data are solely derived from lumbar cerebrospinal fluid (CSF) and mostly originate from single samples. Design We determined concentrations of antiretroviral drugs in serial samples of ventricular CSF and compared these to the concentrations in serum and lumbar CSF of these patients. Methods Two treatment-naive HIV-1-infected patients received external ventricular drainage for obstructive hydrocephalus. Starting with a combination antiretroviral regimen (cART), ventricular CSF, and subsequently lumbar CSF, with parallel serum, was frequently collected. Drug concentrations were determined and CSF-to-serum ratios were calculated. Results High concentrations, resulting in high CSF-to-serum ratios, were found in the ventricular CSF of the three substances zidovudine, lamivudine and indinavir, whereas this was not observed for stavudine, ritonavir, saquinavir and efavirenz. Concentrations of zidovudine and lamivudine were up to four times greater in CSF from the ventricles than in lumbar CSF of the same patient. The zidovudine concentrations in the ventricular CSF exceeded serum concentrations by a factor of 1.4. Conclusion Unexpectedly high concentrations of some antiretrovirals in the ventricular CSF, the site close to the brain parenchyma where HIV is located, should be considered when the cART regimen is aiming at CNS viral replication. |
| Databáze: | OpenAIRE |
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