Bioavailability of Temazepam: Comparison of Four 7.5-mg Capsules with a Single 30-mg Capsule

Abstract

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 (C_max), (3) time to peak concentration (T_max), (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 C_max 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 T_max 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.