Pharmacokinetics

  1. Single-dose administration

When Mecobalamin (METHYCOBAL) was administered orally to healthy adult male volunteers at single doses of 120 mcg and 1,500 mcgnote), the peak serum total vitamin B12 (abbreviated to B12) concentration was reached after 3 hrs. for both doses, and this was dose-dependent. The half-life, increment in the serum total B12 concentration and ΔAUC012 by 12 hrs. after administration are shown in the following figure and table. 40 to 90 percent of the cumulative amount of total B12 excreted in the urine by 24 hrs. after administration was excreted within the 8hrs.

(Note) The approved dosage and administration of mecobalamin are as follows: “The usual adult dose for oral use is 1,500 mcg of mecobalamin daily divided into three doses. The dosage may be adjusted depending on the patient’s age and symptoms.

 

Increment in total serum B12 concentration

 

Dose Tmax (hr) Cmax (pg/mL) ΔCmax (pg/mL) ΔCmax  (%) ΔAUC0-12*1 (pg•hr/mL) T1/2 *2 (hr)
120 mcg 2.8 ± 0.2 743 ± 47 37 ± 15 5.1 ± 2.1 168 ± 58 N.A
1500 mcg 3.6 ± 0.5 972 ± 55 255 ± 51 36.0 ± 7.9 2033 ± 510 12.5
Mean±S.E., n=8
*1 Calculated by the trapezoidal method from the increment in observed 12 hr values, as compared to pre-drug values.
*2 Calculated from the average of 24-48 hr values

 

 

  1. Repeated-dose administration

Mecobalamin (METHYCOBAL) was administered orally to healthy adult male volunteers at a dose of 1,500 mcg daily for 12 consecutive weeks and changes in the serum total B12 concentration were determined until 4 weeks after the last administration. The serum concentration increased for the first 4 weeks after administration, rising to about twice as high as the initial value. Thereafter, there was a gradual increase which peaked at about 2.8 times the initial value at the

12th week of dosing. The serum concentration declined after the last administration (12 weeks), but was still about 1.8 times the initial value 4 weeks after the last administration.