Effect of body position on ventricular CSF methotrexate concentration following intralumbar administration.
OBJECTIVE
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.


CONCLUSIONS
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.
Blaney
S M
SM
Walter Reed Army Medical Center, Washington, DC.
Poplack
D G
DG
Godwin
K
K
McCully
C L
CL
Murphy
R
R
Balis
F M
FM
D000818:Animals; D005260:Female; D007278:Injections, Spinal; D008253:Macaca mulatta; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000134:cerebrospinal fluid*; D011187:Posture; D013997:Time Factors
D008727:Methotrexate