Absence of drug interaction between oral moxifloxacin and intramuscular morphine sulfate in healthy volunteers

Objective: To determine the effects of intramuscular morphine sulfate on th e pharmacokinetics of moxifloxacin. Design: This was a single-centre, randomised, two-way, nonblinded crossover study in healthy young males and females. Participants: 20 healthy volunteers (15 males, five females) with a mean ag e of 34 years were enrolled and considered evaluable for the pharmacokineti c analysis. Methods: Moxifloxacin was given under two conditions separated by a minimum 7-day washout period: alone as a single oral 400mg dose, and immediately f ollowing 10mg of intramuscular morphine sulfate. Concentrations of moxiflox acin in serum were determined by a validated HPLC procedure with fluorescen ce detection. Outcome Measures and Results: Pharmacokinetic parameters estimated were max imum serum concentration (C-max), time to reach C-max(t(max)) area under th e concentration-time curve from zero to infinity (AUC(infinity)), and termi nal elimination half-life (t(1/2)beta). The natural logarithms of AUC(infin ity) and C-max were compared by analysis of variance. The mean moxifloxacin serum concentration vs time profiles were similar between the two treatmen ts. The geometric least square mean C-max values for moxifloxacin were 3.42 mg/L when given alone vs 2.85 mg/L with morphine, producing a ratio (moxif loxacin with morphine vs moxifloxacin alone) of 0.83, with a 90% confidence interval (CI) about the ratio of 0.71 to 0.98. The geometric mean AUC(infi nity) values for moxifloxacin alone and with morphine were 41.5 and 39.6 mg /L.h; the ratio of means was 0.96, with a 90% CI of 0.87 to 1.04. t(max) an d t(1/2)beta values for moxifloxacin were unchanged when coadministered wit h morphine. The single oral dose of moxifloxacin 400mg was well tolerated w hen taken with and without morphine sulfate. Conclusions: Administration of a single intramuscular dose of morphine did not reduce the bioavailability or alter the elimination profile of oral mox ifloxacin. These results suggest that concurrent administration of intramus cular morphine and oral moxifloxacin is unlikely to reduce the efficacy of the quinolone.