We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

To determine if prophylactic etodolac would significantly reduce postendodontic pain, when compared with ibuprofen or placebo, 36 patients consented to single blind oral administration of either 400 mg of etodolac, 600 mg of ibuprofen, or a placebo, before conventional one-appointment root canal therapy. Patient-reported visual analog scale ratings of pain intensity were conducted upon initial clinical presentation, immediately postoperative, 4, 8, 12, 24, 48, and 72 h after initiation of root canal therapy. Results showed that prophylactic ibuprofen administration significantly reduced postendodontic pain at 4 and 8 h after initiation of root canal therapy, when compared with etodolac and a placebo. Patients with a periapical diagnosis of acute apical periodontitis or with a Phoenix abscess showed a significant increased need for additional medication after completion of root canal therapy, compared with all other periapical diagnoses.

The effects of three non-steroidal anti-inflammatory drugs (NSAIDs) on the pharmacokinetics of methotrexate were studied in 10 patients with rheumatoid arthritis.Ketoprofen (3 mg kg-' day-'), flurbiprofen (3 mg kg-' day-'), piroxicam (20 mg day-') or a non-NSAID control (paracetamol/acetaminophen) were administered to patients for at least 6 days (13 days in the case of piroxicam to establish steady state) in a randomized crossover design prior to receiving a weekly oral dose of methotrexate. In the non-NSAID control portion of the study, MTX oral clearance (CLo) was 11.0 ± 3.9 1 h-', renal clearance (CLR) was 7.9 ± 2.8 1 h-1, percent

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Summary. Rats were randomly assigned to treatments: (i) no surgery control; (ii) saline control; (iii) 0\m=.\25,0\m=.\5,1\ m=.\0or 2\m=.\0 \g=m\gnifedipine kg\m=-\1mi n\m=-\1; or (iv) 5\m=.\0 \g=m\g ritodrine kg\m=-\1 min\m=-\1. All drug treatments increased the interval between pup deliveries compared with the no surgery and saline controls. Apparent complete tocolysis was observed in 20, 60, 80 and 80% of the animals receiving 0\m=.\5, 1\m=.\0or 2\m=.\0 \ g=m\ gnifedipine kg\m=-\1 min\m=-\ 1 or 5 \ m=. \ 0\ g=m\ g ritodrine kg\ m=-\ 1 mi n\m=-\1, respectively. A positive pharmacodynamic relationship was observed for the nifedipine doses. Analysis of pup viability showed no statistically significant difference among treatments. Treatment with 2\m=.\0 \g=m\gnifedipine kg\m=-\1 min\m=-\ 1 gave a delay in pup delivery comparable to that with ritodrine.