Secnidazole

Secnidazole is a nitroimidazole antimicrobial drug.

Secnidazole exposure-response relationships and the time course of pharmacodynamic response are unknown.

Cardiac Electrophysiology

The effect of secnidazole on the QTc interval was evaluated in a Phase 1 randomized, double blind, placebo- and positive-controlled four-period crossover thorough QTc study in 52 healthy adult subjects following single oral granule doses of 2 g and 6 g (3-times the recommended dose). Although there was a positive relationship of the QTc interval with secnidazole concentrations, there was no clinically relevant increase in the QTc interval following either dose.

A single oral dose of 2 g of secnidazole in healthy adult female subjects, following an overnight fast and admixed with (4 oz) of applesauce, resulted in a mean (SD) secnidazole peak plasma concentration (C_max) of 45.4 (7.64) mcg/mL and mean (SD) systemic exposure (AUC_0-inf) of 1331.6 (230.16) mcg•hr/mL. Median (range) time to peak concentration (T_max) was 4.0 (3.0-4.0) hours. Following administration of the 2 g dose, mean secnidazole plasma concentrations decreased to 22.1 mcg/mL at 24 hours, 9.2 mcg/mL at 48 hours, 3.8 mcg/mL at 72 hours, and 1.4 mcg/mL at 96 hours.

Absorption

Effect of Food

Administration of 2 g of secnidazole admixed with applesauce followed by ingestion of a high-fat meal (approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories) resulted in no significant change in the rate (C_max) and extent (AUC) of secnidazole exposure as compared to administration when admixed with applesauce and taken under fasted conditions. There was no effect of admixing secnidazole with pudding and yogurt as compared to admixing with applesauce (Table 2).

Table 2. Pharmacokinetic Parameters Following Single Dose Administration of secnidazole 2 g Given Orally:

^* Median (range)
^† Admixed with applesauce

Distribution

The apparent volume of distribution of secnidazole is approximately 42 L. The plasma protein binding of secnidazole is <5%.

Elimination

The total body clearance of secnidazole is approximately 25 mL/min. The renal clearance of secnidazole is approximately 3.9 mL/min.

The plasma elimination half-life for secnidazole is approximately 17 hours.

Metabolism

Secnidazole is metabolized in vitro via oxidation by human hepatic CYP450 enzyme system with ≤1% conversion to metabolites.

Excretion

Approximately 15% of a 2 g oral dose of secnidazole is excreted as unchanged secnidazole in the urine.

Drug Interactions

Oral Contraceptives

Concomitant administration of 2 g of secnidazole with the combination oral contraceptive (OC), ethinyl estradiol (EE) plus norethindrone (NE), to healthy adult female subjects resulted in a decrease in mean C_max of EE of 29%, and no significant effect on the mean AUC of EE. Administration of 2 g of secnidazole 1 day before combination OC administration resulted in no significant effect on mean C_max or AUC of EE.

Concomitant administration of 2 g of secnidazole with the combination OC resulted in no significant effect on mean C_max and AUC of NE (increases of 13% and 16%, respectively). Administration of 2 g of secnidazole 1 day before combination OC administration also resulted in no significant effect on mean C_max and AUC of NE.

Ethanol Metabolism

In vitro studies showed that secnidazole had no effect on aldehyde dehydrogenase activity.