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Effect of body position on ventricular CSF methotrexate concentration following intralumbar administration
S M Blaney1, D G Poplack, K Godwin
1Walter Reed Army Medical Center, Washington, DC.
Purpose:
Intralumbar methotrexate is one of the primary therapeutic modalities for the prevention and treatment of meningeal leukemia. However, methotrexate distribution to the ventricles is limited and highly variable following intralumbar dosing, and cytotoxic concentrations of methotrexate are not always achieved or sustained in the ventricular CSF. We used a nonhuman primate model to determine the effect of body position on the caudal distribution of an intralumbar dose of methotrexate.
Methods:
Methotrexate (1.0 mg) was administered by intralumbar injection to four animals, which were then immediately placed either in an upright sitting position or in a prone position for 1 hour, then upright. Each animal served as its own control and was studied in each position on at least one occasion.
Results:
The mean peak ventricular methotrexate concentration was 0.12 mumol/L (range, 0.091 to 0.20) in animals that were immediately placed upright, compared with 2.81 mumol/L (range, 0.21 to 8.9) in animals that remained prone for 1 hour. The mean area under the concentration-versus-time curves (AUC) was 0.51 mumol/L.h (range, 0.26 to 1.1) in the upright animals and 12.0 mumol/L.h (range, 0.9 to 35.4) in the prone animals.
Conclusion:
Maintaining a prone position for 1 hour after an intralumbar dose increased the peak methotrexate concentration and drug exposure in ventricular CSF. CSF drug distribution following intralumbar therapy can be influenced by body position after the injection.
Insights
Maintaining a prone position after intralumbar methotrexate injection significantly enhances drug distribution to the ventricles. This simple body position adjustment improves therapeutic efficacy for meningeal leukemia treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Intralumbar methotrexate is crucial for treating meningeal leukemia.
- Limited and variable ventricular distribution of methotrexate poses a therapeutic challenge.
- Achieving consistent cytotoxic concentrations in ventricular cerebrospinal fluid (CSF) is difficult.
Purpose of the Study:
- To investigate the impact of body position on the caudal distribution of intralumbar methotrexate.
- To determine if post-injection positioning affects drug concentration in the ventricles.
Main Methods:
- A nonhuman primate model was utilized.
- Methotrexate (1.0 mg) was administered via intralumbar injection.
- Animals were positioned either upright or prone for 1 hour post-injection, with each animal serving as its own control.
Main Results:
- Prone positioning for 1 hour resulted in a 23-fold increase in mean peak ventricular methotrexate concentration (2.81 mumol/L vs. 0.12 mumol/L).
- The mean area under the concentration-time curve (AUC) was significantly higher in the prone group (12.0 mumol/L.h vs. 0.51 mumol/L.h).
- Drug exposure in ventricular CSF was substantially enhanced by maintaining a prone position.
Conclusions:
- Maintaining a prone position for 1 hour post-intralumbar methotrexate administration significantly increases peak concentration and overall drug exposure in the ventricular CSF.
- Body position is a critical factor influencing CSF drug distribution after intralumbar therapy.
- This finding suggests a simple, non-invasive method to optimize methotrexate delivery for meningeal leukemia treatment.