* Median (range) † Baseline corrected values  

 

BONJESTA 

Mean±SD 

 

 

AUC0-24 

(ng•h/mL)  

 

AUC0-12 

(ng•h/mL)  

 

AUC0-6 

(ng•h/mL)  

 

Cmax 

(ng/mL)  

 

Tmax* 

(h)  

 

Doxylamine 

 N=34 2879.4 ±

696.0 1573.2 ±

406.5 883.6 ±

228.5 173.6 ±

45.5 3.5

(1.0-20.0) 

 

Pyridoxine 

 N=34 80.0 ±

22.7 46.3 ±

15.4 45.3 ±

16.3 48.2 ±

23.7 1.5

(0.3-16.5) 

 

Pyridoxal† 

 N=34 1511.3 ±

300.0 848.1 ±

183.6 647.2 ±

149.6 189.6 ±

48.3 3.0

(2.0-15.0) 

 

Pyridoxal 5′-Phosphate† 

 N=34 1742.3 ±

554.3 831.7 ±

274.5 426.2 ±

144.0 85.9 ±

26.2 15.0

(2.0-24.0) 

 

Food Effect 

 

In a single-dose, crossover clinical trial conducted in 23 healthy, premenopausal women, the administration of a high fat, high calorie meal delayed the absorption of doxylamine, pyridoxine, and pyridoxine metabolites. This delay is associated with lower peak concentrations of doxylamine, pyridoxine, and pyridoxal. The extent of absorption for pyridoxine was decreased.

 

The effect of food on the peak concentration and the extent of absorption of the pyridoxine component is more complex because the pyridoxine metabolites such as pyridoxal, pyridoxamine, pyridoxal 5′-phosphate, and pyridoxamine 5′-phosphate also contribute to the biological activity. Food significantly reduces the bioavailability of pyridoxine, lowering its Cmax and AUC by approximately 67% and 37%, respectively, compared to fasting conditions. Similarly, food significantly reduces pyridoxal Cmax by approximately 46% compared to fasting conditions. In contrast, food did not affect pyridoxal 5′-phosphate Cmax and AUC. 

 

Table 4 – Mean ± SD Pharmacokinetic Parameters of Doxylamine and Pyridoxine Metabolites Following a Single Dose Administration of BONJESTA Under Fed and Fasted Conditions in Healthy Premenopausal Adult Women 

 

* Profile of Subject 20 was excluded † Median (range) ‡ Baseline corrected values  

BONJESTA

N=23 

 AUC0-t (ng•h/mL) AUC0-inf (ng•h/mL) Cmax 

(ng/mL) Tmax*,† 

 (h) T1/2el 

 (h) 

Doxylamine 

Mean±SD Fasted 1273.7 ±

276.2 1321.9 ±

315.5 85.9 ±

10.6 3.5

(2.5-5.5) 11.9 ±

2.2 

Fed 1242.8 ±

254.0 1281.4 ±

282.9 64.5 ±

15.2 6.5

(2.0-24.0) 12.7 ±

2.60 

Pyridoxine 

Mean±SD Fasted 34.7 ±