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R Tackett

Publications and source records attributed to R Tackett.

5 recordsLinked to original sources

Zidovudine serum, cerebrospinal fluid, and brain concentrations following chronic administration of a new zidovudine formulation via an implantable pump in dogs [corrected].

Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) by continuous infusion via an implantable pump in dogs. The AZT serum and cerebrospinal fluid (CSF) concentrations were measured over a 28-day treatment period by HPLC. Terminal brain AZT concentrations were also measured. Control (vehicle only) animals were also studied. All animals were evaluated for pathological changes associated with the AZT and vehicle infusions in catheterized vessels and other organs. In the iv AZT treatment group, serum AZT concentrations were relatively constant, with individual coefficients of variations (%CV) of 20% or less. Mean CSF:serum and brain:serum AZT concentration ratios were 0.149 and 0.212, respectively. In the ia AZT treatment group, serum AZT concentrations were more variable than in the iv group, with %CV ranging from 22 to 79%. The fluctuations in serum concentrations were attributed to temporary blockages of the outflow catheter. Mean CSF:serum and brain:serum AZT concentration ratios were 0.126 and 0.249, respectively. Pathological changes, similar in both control and treatment groups, included endothelial denudation and myointimal proliferation at the infusion sites. The conclusions of the study are (1) steady-state greater than 1 microM AZT serum concentrations can be maintained chronically by use of an implantable pump containing a basic pH AZT solution; (2) ia delivery of AZT did not increase central nervous system uptake compared with iv administration; and (3) morbidity associated with the infused solutions does not seem to be a limitation for this mode of therapy.

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Picogram detection of eicosanoids by ultraviolet absorbance after narrow-bore high-performance liquid chromatography. Comparison with conventional-bore column.

Mobile-phase variations were employed to achieve optimal separation by narrow-bore reversed-phase high-performance liquid chromatography of eleven eicosanoids. Separation and quantitation by ultraviolet absorbance at 190 nm using conventional-bore ODS columns were compared. Using the improved sensitivity obtained by means of the narrow-bore column, i.e. 250-pg detection limits of a standard solution, analysis of eicosanoids in kidney medulla was achieved. Parallel quantitation by radioactivity, using [1-(14)C]arachidonic acid as substrate, was applied.

Animals↗