Bioavailability of temazepam: comparison of four 7.5-MG capsules with a single 30-MG capsule.

OBJECTIVE

To compare the bioavailability of four temazepam 7.5-mg capsules (Restoril, Sandoz Pharmaceuticals) with that of a single temazepam 30-mg capsule.

DESIGN

Single-dose, open-label, two-period, crossover (replicated Latin square).

SETTING

Domiciled environment for clinical testing.

PARTICIPANTS

Twenty-six healthy male volunteers aged 18-40 years; 25 completed the study.

INTERVENTIONS

Subjects randomly received either four temazepam 7.5-mg capsules or one temazepam 30-mg capsule. Blood samples were drawn at various time points after each period (0-48 h), and analyzed for plasma concentration of temazepam. The washout period between doses was five days.

MAIN OUTCOME MEASUREMENTS

Five parameters of both dosage forms were compared: (1) area under curve (AUC), (2) peak concentration (Cmax), (3) time to peak concentration (Tmax), (4) apparent rate constant for absorption, and (5) lag time for appearance of drug in plasma. Statistical procedures included ANOVA, power analysis, and confidence limits.

RESULTS

The mean AUC for the four 7.5-mg capsules and one 30-mg capsule differed by less than 2 percent and the mean Cmax differed by less than 14 percent for the two dosage strengths; neither of these differences reached statistical significance (p > 0.05). The 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form (mean Tmax 1.18 and 1.73 h, respectively; p = 0.01).

CONCLUSIONS

The two formulations of temazepam were bioequivalent with respect to the extent of bioavailability. Regarding the rate of absorption, however, the 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form.