Pyridoxine Hydrochloride 

 

Pyridoxine hydrochloride is a vitamin B6 analog. The chemical name for pyridoxine hydrochloride is 3,4-pyridinedimethanol, 5-hydroxy-6-methyl-, hydrochloride. The empirical formula is C8H11NO3 • HCl and the molecular mass is 205.64. The structural formula is:

 

structure-2 

 

Pyridoxine hydrochloride is a white or practically white crystalline powder that is freely soluble in water, slightly soluble in alcohol and insoluble in ether.

 

12 CLINICAL PHARMACOLOGY

 

12.1 Mechanism of Action

 

The mechanism of action of BONJESTA is unknown.

 

12.3 Pharmacokinetics

 

The pharmacokinetics of BONJESTA has been characterized in healthy non-pregnant adult women.

 

Absorption 

 

In a single-dose, crossover clinical trial conducted in 48 healthy, premenopausal women under fasting conditions, one BONJESTA (20 mg doxylamine succinate and 20 mg pyridoxine) tablet was bioequivalent to two combination tablets of 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride based on the exposure (AUC) and peak concentration (Cmax) of doxylamine and baseline corrected pyridoxal 5′-phosphate. Mean ± SD plasma (whole blood for pyridoxal) pharmacokinetic (PK) parameters are summarized in Table 2.

 

Table 2 – Mean ± SD Single-Dose Pharmacokinetics of BONJESTA in Healthy Premenopausal Adult Women 

 

* Median (range) † Baseline corrected values ‡ N=46 for AUC 0-inf  

 

BONJESTA 

Mean±SD 

 

AUC0-t 

(ng•h/mL)  

 

AUC0-inf 

(ng•h/mL)  

 

AUC0-72 

(ng•h/mL)  

 

Cmax 

(ng/mL)  

 

Tmax* 

(h)  

 

Doxylamine 

 N=48 1367.0 ±

356.7 1425.8 ±

405.1 --- 92.3 ±

15.7 4.5

(2.5-5.5) 

Pyridoxine 

 N=47 42.3 ±

14.7 42.5 ±

14.7 --- 47.1 ±

18.7 0.5

(0.5-4.7) 

Pyridoxal† 

 N=48‡ 203.7 ±

51.7 233.6 ±

55.9 --- 58.9 ±

17.0 3.0

(0.8-5.0) 

Pyridoxal 5′-Phosphate† 

 N=48 --- --- 1076.2 ±

382.2 30.1 ±

9.2 9.0

(3.0-16.0) 

In a multiple-dose, crossover clinical trial conducted in 31 healthy, premenopausal women, one BONJESTA (20 mg doxylamine succinate and 20 mg pyridoxine) tablet given twice daily for 11 days was bioequivalent to one combination tablet of 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride given three times daily (1 tablet in the morning, 1 tablet in the afternoon and 2 tablets at bedtime), based on the exposure (AUC) and peak concentration (Cmax) of doxylamine and baseline corrected pyridoxal 5′-phosphate. Mean ± SD plasma (whole blood for pyridoxal) PK parameters are summarized in Table 3.