A COMPARISON OF LOW-DOSE METHOTREXATE BIOAVAILABILITY - ORAL SOLUTION, ORAL TABLET, SUBCUTANEOUS AND INTRAMUSCULAR DOSING

Objective. To compare the relative bioavailability of low dose methotr exate (MTX) administered as tablet, oral solution, and subcutaneous (s c) injection to that of intramuscular (im) injection in patients with rheumatoid arthritis (RA). Methods. Twelve patients meeting the Americ an College of Rheumatology criteria for RA had serial blood MTX concen tration samples drawn over a 24-h period after receiving their normal weekly MTX dose. Relative bioavailability (F) of the tablet and oral s olution formulations was determined by comparison of the area under th e time-versus-serum-concentration curves (AUC) for the 2 different ora l formulations as a percentage of the AUC for im injection. Also, rela tive bioavailability of the sc formulation was compared to im in 6 of the patients. Results. Mean F for the oral tablet was 0.85, while that for the oral solution was 0.87. Both oral formulations showed a stati stically significant difference in mean F when compared to im (tablet vs im, p = 0.002, oral solution vs im, p = 0.009). No statistically si gnificant difference, however, was found in mean relative bioavailabil ity between tablet and solution (p = 0.744). The mean F for sc was 0.9 7; no statistically significant difference existed between the mean F values for the sc and im routes of administration (p = 0.657). Conclus ions. Our data suggest the oral solution may be substituted for tablet dosing and sc injection substituted for im. Thus, a variety of differ ent dosing methodologies may be considered providing the most appropri ate route in each patient, given issues of compliance, medication cost , and preference.