D-Ma2, D-Leu51Enkephalin (DADLE) labelled with tritium in the 2,6-positions of N-terminus tyrosine residue has been prepared. Synthesis of the precursor peptide, [2,6-dibromo-Tyrl]DADLE, was performed by solid phase synthesis using F'moc strategy. The peptide was tritiated catalytically to yield [2
Cerebrospinal fluid pharmacokinetics of intrathecal morphine sulfate and D-Ala2-D-Leu5-enkephalin
β Scribed by Dwight E. Moulin; Charles E. Inturrisi; Dr Kathleen M. Foley
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- English
- Weight
- 488 KB
- Volume
- 20
- Category
- Article
- ISSN
- 0364-5134
No coin nor oath required. For personal study only.
β¦ Synopsis
Using an implantable pump system to deliver drugs and sample cerebrospinal fluid (CSF), we assessed rostral redistribution and systemic uptake after intrathecal bolus injection and steady-state infusion of morphine sulfate and the opioid peptide ~A l a ~-~L e u ~-e n k e p h a l i n (DADL) in two patients. Following bolus injection, the mean CSF elimination half-lives for morphine sulfate and DADL were 94 and 115 minutes, respectively. With the catheter tip at L2, the ratio of lumbar to cisternal (L/C) concentrations of morphine sulfate was about 7:1, and with the catheter tip at T10, the L/C ratios of morphine sulfate and DADL were approximately 2:1, indicating that this ratio is dependent in part on the level of intrathecal drug administration. CSF levels of morphine sulfate at steady state were three orders of magnitude higher than those in plasma. The CSF pharmacokinetics of morphine sulfate and DADL are similar, with supraspinal redistribution of these opioids via the CSF likely playing an important role in the generation of analgesia and central nervous system side effects.
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