OBJECTIVE: To investigate penetration of zidovudine (ZDV) into the cerebrospinal fluid (CSF) of HIV-infected patients for whom a lumbar puncture was indicated. DESIGN: A prospective study. SETTING: General 525-bed hospital with special funding for treatment and research of HIV-infected patients. PATIENTS, PARTICIPANTS: Thirty-nine patients with a medical indication for lumbar puncture who used ZDV chronically were included in this study (50 samples in total). MAIN OUTCOME MEASURE: Determination of ZDV and proteins in CSF and plasma samples. RESULTS: CSF concentrations of ZDV showed little fluctuation 1-8 h after the last ingestion of ZDV. In contrast, plasma levels displayed large variability in this period and decreased exponentially over time. As a result, the CSF/plasma ratio increased linearly over time. No significant relation between the ZDV dose, neither the medical indication for lumbar puncture nor the protein ratio (as a measure for the integrity of the blood-brain barrier), and CSF levels of ZDV was found. The CSF/plasma ratio of ZDV did not give essential information on drug distribution into CSF. CONCLUSIONS: Penetration of ZDV into the CSF appears to be independent of the dose (range, 200-1250 mg daily), which may be an explanation for the efficacy of low doses of ZDV in the prevention and treatment of HIV-related neurological diseases. ZDV levels were at steady-state during the first 6 h after ingestion. The CSF/plasma ratio of ZDV concentrations is not an appropriate marker for drug penetration into CSF.
OBJECTIVE: To investigate penetration of zidovudine (ZDV) into the cerebrospinal fluid (CSF) of HIV-infectedpatients for whom a lumbar puncture was indicated. DESIGN: A prospective study. SETTING: General 525-bed hospital with special funding for treatment and research of HIV-infectedpatients. PATIENTS, PARTICIPANTS: Thirty-nine patients with a medical indication for lumbar puncture who used ZDV chronically were included in this study (50 samples in total). MAIN OUTCOME MEASURE: Determination of ZDV and proteins in CSF and plasma samples. RESULTS: CSF concentrations of ZDV showed little fluctuation 1-8 h after the last ingestion of ZDV. In contrast, plasma levels displayed large variability in this period and decreased exponentially over time. As a result, the CSF/plasma ratio increased linearly over time. No significant relation between the ZDV dose, neither the medical indication for lumbar puncture nor the protein ratio (as a measure for the integrity of the blood-brain barrier), and CSF levels of ZDV was found. The CSF/plasma ratio of ZDV did not give essential information on drug distribution into CSF. CONCLUSIONS: Penetration of ZDV into the CSF appears to be independent of the dose (range, 200-1250 mg daily), which may be an explanation for the efficacy of low doses of ZDV in the prevention and treatment of HIV-related neurological diseases. ZDV levels were at steady-state during the first 6 h after ingestion. The CSF/plasma ratio of ZDV concentrations is not an appropriate marker for drug penetration into CSF.
Authors: Ghazia Asif; Selwyn J Hurwitz; Aleksandr Obikhod; David Delinsky; Janarthanan Narayanasamy; Chung K Chu; Harold M McClure; Raymond F Schinazi Journal: Antimicrob Agents Chemother Date: 2007-05-07 Impact factor: 5.191
Authors: Huachun Chen; S Balakrishna Pai; Selwyn J Hurwitz; Chung K Chu; Yuliya Glazkova; Harold M McClure; Mark Feitelson; Raymond F Schinazi Journal: Antimicrob Agents Chemother Date: 2003-06 Impact factor: 5.191
Authors: Aylin Yilmaz; Arash Izadkhashti; Richard W Price; Patrick W Mallon; Marc De Meulder; Philip Timmerman; Magnus Gisslén Journal: AIDS Res Hum Retroviruses Date: 2009-04 Impact factor: 2.205