Comparative bioavailability and safety of two intramuscular ceftriaxone formulations.

OBJECTIVE

To determine if two ceftriaxone solutions of different concentrations are bioequivalent when administered intramuscularly.

DESIGN

Double-blind, single-dose, two-period, randomized crossover study.

SETTING

A clinical research center.

SUBJECTS

Seventeen healthy volunteers.

INTERVENTION

Ceftriaxone 500 mg administered in either 2 or 1.4 mL of lidocaine 1% solution, with final ceftriaxone concentrations of 250 and 350 mg/mL, respectively.

MAIN OUTCOME MEASURES

Blood samples were assayed for ceftriaxone concentrations with HPLC and pharmacokinetic parameters were calculated from the resulting plasma-concentration time profiles: maximum plasma concentration (Cmax) of ceftriaxone and areas under the concentration-time curve (AUC) from 0 to 36 h and 0 to infinity were the primary parameters considered in the determination of bioequivalence.

RESULTS

The two solutions were generally well tolerated and had similar safety profiles. Administration of both solutions resulted in similar mean values for all pharmacokinetic parameters. Statistical analysis showed no significant differences between the two solutions in any pharmacokinetic parameter, indicating that the two solutions are statistically bioequivalent (p < or = 0.05). The 90% CI for the ratio of the means for AUC0-36 (0.86 to 1.11), AUC0.36 (0.89 to 1.14), and Cmax (0.84 to 1.12) are within the Food and Drug Administration range of bioequivalence (0.80 to 1.25).

CONCLUSIONS

These results demonstrate that the more concentrated solution of ceftriaxone (350 mg/mL) is bioequivalent to the currently marketed solution of 250 mg/mL.