A significant methotrexate-glutamine pharmacokinetic interaction.
Previous studies indicate that glutamine-supplemented diets decrease the enterocolitis associated with methotrexate administration. The influence of glutamine on the pharmacokinetics of methotrexate and the formation of its major hepatic metabolite, 7-hydroxy-methotrexate was examined in 36 adult, female Lewis rats. Animals were randomly assigned to receive either a 3% glycine-supplemented solid diet (GLY; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) or a 3% glutamine-supplemented solid diet (GLN; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) ad libitum for 35 days. Animals were separated into two groups (serum methotrexate pharmacokinetics, n = 20; or methotrexate renal elimination, n = 16) and given a 10 mg/kg dose of methotrexate. There was a 25% decrease in mean methotrexate total serum clearance in the GLN group compared with the control group (0.63 +/- 0.09 L.h-1.kg-1 and 0.47 +/- 0.13 L.h-1.kg-1, respectively, p = 0.01). Renal methotrexate elimination was decreased by 65%. There was no significant difference in methotrexate volume of distribution or half-life between the two groups. Glutamine decreases methotrexate systemic clearance, thus exposing the host as well as the tumor to greater methotrexate concentrations.
Charland
S L
SL
Department of Pharmacy Practice and Administration, Philadelphia College of Pharmacy and Science, Pennsylvania, USA.
Bartlett
D L
DL
Torosian
M H
MH
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004760:Enterocolitis / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D015994:Incidence; D007275:Injections, Intravenous; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D005973:Glutamine; D008727:Methotrexate