Literature DB >> 8597780

Study on didanosine concentrations in cerebrospinal fluid. Implications for the treatment and prevention of AIDS dementia complex.

D M Burger1, C L Kraayeveld, P L Meenhorst, J W Mulder, R M Hoetelmans, C H Koks, J H Beijnen.   

Abstract

It has been hypothesized that didanosine has a low efficacy in the prevention and treatment of patients with the dementia complex of acquired immunodeficiency syndrome (AIDS) because "... the drug has not been detected in the cerebrospinal fluid". We investigated didanosine concentrations in cerebrospinal fluid (CSF) and plasma of four patients with AIDS who were using didanosine chronically. Didanosine levels, 4 h after the last drug administration, averaged 0.16 (+/- 0.03) mumol/l in CSF and 0.70 (+/- 0.27) mumol/l in plasma. When compared with historical data from patients using zidovudine, didanosine concentrations in CSF appeared to be approximately half (on a molar base) those of zidovudine concentrations in the CSF. Whether this difference in CSF levels is the explanation for the presumed lower efficacy of didanosine in the prevention and treatment of AIDS dementia complex remains to be proven. However, it is clear from this study, in contrast with earlier suggestions, that didanosine is able to pass the blood-CSF barrier in human immunodeficiency virus-infected individuals.

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Year:  1995        PMID: 8597780     DOI: 10.1007/bf01870615

Source DB:  PubMed          Journal:  Pharm World Sci        ISSN: 0928-1231


  23 in total

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2.  Neuropathological evidence that zidovudine reduces incidence of HIV infection of brain.

Authors:  F Gray; C Geny; E Dournon; F Fenelon; F Lionnet; R Gherardi
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3.  Clinical pharmacology of 2',3'-dideoxyinosine in human immunodeficiency virus-infected children.

Authors:  F M Balis; P A Pizzo; K M Butler; M E Hawkins; P Brouwers; R N Husson; F Jacobsen; S M Blaney; J Gress; P Jarosinski
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4.  Pharmacokinetics of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine in patients with severe human immunodeficiency virus infection.

Authors:  N R Hartman; R Yarchoan; J M Pluda; R V Thomas; K S Marczyk; S Broder; D G Johns
Journal:  Clin Pharmacol Ther       Date:  1990-05       Impact factor: 6.875

5.  Reduced frequency of HIV-induced brain lesions in AIDS patients treated with zidovudine.

Authors:  L Vago; A Castagna; A Lazzarin; G Trabattoni; P Cinque; G Costanzi
Journal:  J Acquir Immune Defic Syndr (1988)       Date:  1993-01

6.  AIDS dementia complex and didanosine.

Authors:  P Portegies; R H Enting; M D de Jong; S A Danner; P Reiss; J Goudsmit; J M Lange
Journal:  Lancet       Date:  1994-09-10       Impact factor: 79.321

7.  In vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine.

Authors:  R Yarchoan; H Mitsuya; R V Thomas; J M Pluda; N R Hartman; C F Perno; K S Marczyk; J P Allain; D G Johns; S Broder
Journal:  Science       Date:  1989-07-28       Impact factor: 47.728

8.  Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group.

Authors:  J J Sidtis; C Gatsonis; R W Price; E J Singer; A C Collier; D D Richman; M S Hirsch; F W Schaerf; M A Fischl; K Kieburtz
Journal:  Ann Neurol       Date:  1993-04       Impact factor: 10.422

9.  Probenecid enhances central nervous system uptake of 2',3'-dideoxyinosine by inhibiting cerebrospinal fluid efflux.

Authors:  R E Galinsky; K K Flaharty; B L Hoesterey; B D Anderson
Journal:  J Pharmacol Exp Ther       Date:  1991-06       Impact factor: 4.030

10.  Central nervous system targeting of 2',3'-dideoxyinosine via adenosine deaminase-activated 6-halo-dideoxypurine prodrugs.

Authors:  M E Morgan; S C Chi; K Murakami; H Mitsuya; B D Anderson
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  7 in total

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2.  Selective inhibition of syncytium-inducing and nonsyncytium-inducing HIV-1 variants in individuals receiving didanosine or zidovudine, respectively.

Authors:  A B van't Wout; L J Ran; M D de Jong; M Bakker; R van Leeuwen; D W Notermans; A E Loeliger; F de Wolf; S A Danner; P Reiss; C A Boucher; J M Lange; H Schuitemaker
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Journal:  Arch Neurol       Date:  2008-01

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Review 5.  Clinical implications of CNS penetration of antiretroviral drugs.

Authors:  Heather E Wynn; Richard C Brundage; Courtney V Fletcher
Journal:  CNS Drugs       Date:  2002       Impact factor: 5.749

Review 6.  How much do antiretroviral drugs penetrate into the central nervous system?

Authors:  L Ene; D Duiculescu; S M Ruta
Journal:  J Med Life       Date:  2011-11-24

Review 7.  Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals.

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  7 in total

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