Pharmacokinetics of
levonorgestrel(LNG )in the form of injectable
microspheres made of
biodegradable co-polymer of polylactic acid and polyglycolic acid(9:1
PLGA)that contained 17.76%LNG,were tested in rats.Rats were given a
single intramuscular injection(im )of LNG microspheres at doses of
20.4,41.1 and 83.3 mg·kg-1.Six
rats were treated with a single im of
LNG
microcrystals at
dose of 35.0 mg·kg-1.Plasma samples obtained
before injection and at various time after injection were analyzed
for LNG by RIA method. eak
Plasma LNG level of 67.66 nmol·L-1 was
obtained 4.88 h after im of LNG microcrystals, T1/2=5.78d, MRT=10.
16 d and T<0.32 nmol·L-1=41.50d. Plasma LNG levels among rats after
im of three different doses of LNG microspheres showed simi- lar
biphasic changes.Cmaxl(the first phase)were 15.19,33.61 and 38.55
nmol·L-1;TP1 Were 6,4.67 and 4.33 h;Ctrough Were 1.21,4.36 and 9.06
nmol·L-1;Ttrough Were 55,53.67 and 54. 83 d;Cmax2(the second
phase)were 3.80,9.48 and 19.68 nmol·L-1;Tp2were 100.49,102.21 and
89.27 d;AUC were 440.27,1082.82 and 1931. 47 nmol·d·L-1; MRT were
69.23,65.12 and 68.25d;T<0.32nmol·L-1 Were 167.81,169.73 and 167.23
d after im of LNG microspheres in doses of 20.4, 41.1 and 83.3
mg(LNG)· kg-1 , respectively·Cmax1,Ctrough,Cmax2 and AUC showed
significantly positive correlation with LNG dose, while
Tp1,Lp2,Ttrough,MRT and T<0.32nmol·L-1 did not. The first
phase peak
plasma LNG levels of LNG microspheres were significantly lower than
that of LNG microcrystals ,but MRT and T< 0.32nmol·L-1 were
significantly longer than that of LNG microcrystals. Pharmacokinetics
of LNG microspheres in rats indicate that 9 :1 PLGA microspheres
containing LNG have remarkablely long-acting sustained release
action.
More abstracts about the PHARMACOKINETICS OF LEVONORGESTREL AFTER A SINGLE DOSE OF
BIODEGRADABLE MICROSPHERES CONTAINING