Efflux of Zidovudine and 2′,3′-Dideoxyinosine Out of the Cerebrospinal Fluid When Administered Alone and in Combination to Macaca nemestrina View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1994-02

AUTHORS

Tove Tuntland, Rashid J. Ravasco, Sayed Al-Habet, Jashvant D. Unadkat

ABSTRACT

To determine if there is active efflux of zidovudine (ZDV) and 2′,3′-dideoxyinosine (ddl) out of the cerebrospinal fluid (CSF), and if this efflux is saturable, we investigated the steady-state CSF/plasma concentration ratio of the two drugs when administered alone or in combination. Constant-rate infusions of ZDV, ddl or both were administered to seven macaques (Macaca nemestrina) through a chronic venous catheter for a minimum of 28 hr. Antipyrine, a marker of passive diffusion, was coinfused in all experiments. Blood (5 mL) and CSF samples (0.5–1 mL) were collected by venous and lumbar/thoracic punctures, respectively, at 24 and 28 hr after beginning the infusion. When ZDV and ddl were administered alone, the steady-state CSF/plasma concentration ratios were significantly different from unity (ZDV, 0.20 ± 0.08; ddI, 0.09 ± 0.04) and were independent of the plasma concentration (P > 0.05). In contrast, the CSF/plasma concentration ratio of antipyrine (0.82 ± 0.19) was close but significantly smaller than unity (P > 0.05). The CSF/ plasma concentration ratios after simultaneous administration of ZDV and ddI were not significantly different (P > 0.05) from those obtained after administration of the drugs alone. These results suggest that ZDV and ddI are actively transported out of the CSF; however, within the concentration range studied, this efflux is neither saturable nor mutually competitive. Concomitant administration of ZDV and ddI did not produce a systemic interaction in the animals, indicating that the pharmacokinetics of either drug is unaffected by the presence of the other. More... »

PAGES

312-317

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1018928013044

DOI

http://dx.doi.org/10.1023/a:1018928013044

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050688861

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8165194


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