Bioavailability study with 2 different levonorgestrel-containing drugs in women.
In a randomized, single dose, open crossover study in 24 healthy women, aged between 20 and 28 years, the relative bioavailability of the test product Mini 30 (0.03 mg levonorgestrel) in comparison to a reference, Microval, was investigated after single dose administration. Because there was a difference in the in vitro dissolution test, it was of interest whether this difference had an influence on the extent and rate of absorption. Whereas 99.4% of the test were dissolved after 20 minutes, only 48.3% of the reference were dissolved after 45 minutes, 74.8% after 120 minutes and 95.5% after 240 minutes. Blood samples were taken from time 0-72 hours after administration. All serum samples were analyzed twice in a radioimmunoassay which was validated before the start of the study. The limit of quantitation was at 50 pg/ml. The AUC0 -infinity ratio test/reference and the 90% confidence interval were 104.8%, and 99.10%, respectively. The Cmax ratio test/reference and the 90% confidence interval were 175.5%, and 159.8%-192.8%, respectively. With regard to the extent of absorption (AUC0-infinity) the 2 preparations were within the acceptance range for bioequivalence whereas they were outside the acceptance range for the rate of absorption (Cmax). The elimination half-lives of LNG did not differ between the test and reference preparations (25.08 +/- 11.94 h, and 25.70 +/- 10.08 h, respectively). So, the in vitro results concerning the rate of dissolution were confirmed by the in vivo findings in Cmax whereas regarding the extent of absorption (AUC) there were no differences between the 2 preparations.
Nassr
N
N
Institute of Clinical Pharmacology, Friedrich Schiller University, Jena, Germany.
Farker
K
K
Lautenschlager
M
M
Nagel
U
U
Zimmermann
H
H
Mellinger
U
U
Hoffmann
A
A
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D005858:Germany; D006207:Half-Life; D006801:Humans; D007553:Isotope Labeling; D016912:Levonorgestrel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D012015:Reference Standards; D013810:Therapeutic Equivalency
D045167:Progesterone Congeners; D016912:Levonorgestrel