[Pharmacokinetics of levonorgestrel after a single dose of biodegradable microspheres containing levonorgestrel in...

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. Peak plasma LNG level of 67.66 nmol.L-1 was obtained 4.88 h after im of LNG microcrystals, T1/2 = 5.78 d, MRT = 10.16 d and T < 0.32 nmol.L-1 = 41.50 d. Plasma LNG levels among rats after im of three different doses of LNG microspheres showed similar biphasic changes. Cmax1 (the first phase) were 15.19, 33.61 and 38.55 nmol.L-1; Tp1 were 6, 4.67 and 4.33h; 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; Tp2 were 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 63.25 d; T < 0.32 nmol.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, Tp2, Ttrough, MRT and T < 0.32 nmol.L-1 did not.(ABSTRACT TRUNCATED AT 250 WORDS)