Pharmacokinetics of norethindrone: effect of particle size.
In 24 healthy women between the ages of 19 and 35 years who had not used oral contraceptive preparations for at least 60 days, it was found that the smaller the particle size of norethindrone (NET) administered, the higher was the plasma NET level obtained. Three different preparations having particle sizes of NET smaller than 250 microns, 44 microns or 10 microns were tested in a crossover pattern. The time required to reach maximum plasma concentration (Tmax) became shorter with decreasing particle size, 1.69 hr, 1.52 hr and 1.06 hr, respectively. As particle size was reduced, the maximum NET plasma concentration (Cmax) increased for the 3 different 1 mg NET preparations, i.e. 8.66 ng/ml, 10.53 ng/ml and 15.73 ng/ml. A trial with a 2 mg NET preparation made with NET utilizing the 44 microns same material displayed a Tmax similar to the 1 mg NET preparation having the same particle size while the Cmax reached a level of 17.56 ng/ml. The area under the plasma concentration versus time curve from 0-24 hrs and the extrapolated total area under the curve, increased with decreasing particle size. The use of a smaller particle size allows for more rapid dissolution or oral contraceptive tablets when measured in vitro; however, there is no evidence that such faster dissolution leads to a significant difference in efficacy. Oral contraceptive tablets have, since their inception, utilized both large and small NET particle size material in various preparations.
Saperstein
S
S
Syntex Laboratories, Inc., Palo Alto, CA 94304.
Edgren
R A
RA
Jung
D
D
Mroszczak
E J
EJ
Lee
G J
GJ
Dorr
A
A
Pritchard
R
R
Kushinsky
S
S
Fong
J C
JC
Combs
D L
DL
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000493:pharmacokinetics*; D010316:Particle Size
D009640:Norethindrone