To study the bioequivalence of a kind of progesterone sustained release suppository, a randomized cross-over study was conducted in 12 rabbits. A single rectal dose of 2.75 mg/kg progesterone sustained released suppository (tested formulation, T) and progesterone suppository (reference formulation, R) was administered; a multiple dose of 2.75 mg/kg was given up to seven times with an interval of 8 h. Concentrations in serum were determined by a competitive enzyme immunoassay. The main parameters of T were: for single and multiple doses, Cmax was 48.8 +/- 11.8 ng/mL and 43.5 +/- 9.4 ng/mL, Tmax was 0.5 +/- 0.3 h and 0.4 +/- 0.3 h, AUC(0-24 h) was 362.4 +/- 143 ng x h x mL(-1) and 310.6 +/- 70.3 ng x h x mL(-1), respectively. The relative bioavailability of T to R were (104.2 +/- 13.4)% and (111.4 +/- 19.1)%, respectively. Statistical analysis showed that the two formulations were bioequivalent and T had sustained released feature.
Administration, Rectal ; Biological Availability ; Cross-Over Studies ; Progesterone/administration & dosage ; Progesterone/*pharmacokinetics ; Random Allocation ; Suppositories

AIMTo quantify progesterone (P) and one of its metabolites 20alpha-hydroxy-4-pregnen-3-one (20alpha-OHP) in rat plasma and uterus after im administration of progesterone.

METHODSPlasma and uterus samples were prepared by liquid-liquid extraction and separated through Shimadzu VP-ODS column (150 mm x 4.6 mm ID, 5 microm). The mobile phase consisted of acetonitrile and water (60: 40, adjusted to pH 4.0 with phosphoric acid). The detector was set at 240 nm. Norgestrel was used as the internal standard.

RESULTSCmax of P in plasma was (508 +/- 62) microg x L(-1), Tmax was (3.2 +/- 0.4) h, T1/2 (ke) was (10 +/- 4) h and mean AUC0-48h was (5886 +/- 1573) microg x L(-1) x h. The maximum concentration of P in uterus was (1.7 +/- 1.1) microg x g(-1) and the peak time was (5.2 +/- 1.11) h. 20alpha-OHP showed a similar Tmax with P.

CONCLUSIONThe method is accurate and convenient. It can be used to determine P and its main metabolite 20alpha-OHP simultaneously for studying their preclinical pharmacokinetics.

20-alpha-Dihydroprogesterone ; blood ; pharmacokinetics ; Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Female ; Injections, Intramuscular ; Progesterone ; blood ; metabolism ; pharmacokinetics ; Rats ; Rats, Wistar ; Uterus ; metabolism

OBJECTIVETo establish a RP-HPLC method for determination of plasma progesterone and to apply the method for pharmacokinetics study of progesterone-loaded lipid nanoparticles after oral administration in rats.

METHODSThe plasma samples were collected from castrated rat after oral administration of progesterone-loaded lipid nanoparticles and extracted by acetic ether. The determination was performed on a Hypersil C18 column (150 mm X 3.9 mm , 5 microm) with a mobile phase consisting of methanol and water (60:40) at a flow-rate of 0.6 ml/min. The UV detector was at 240 nm and danazol was used as internal standard.

RESULTGood linearity was obtained over the range of 0.02-2 microg/ml progesterone in plasma(r=0.9999, n=3). The quantification limit was (0.02 +/-0.004) microg/ml(n=3) and the limit of detection was 0.005 microg.mL(-1)(S/N = or >3). The inter-and intra-day RSDs were all less than 10% for quality control samples at high-, medium- and low-concentrations. The average absolute recovery rate was 90.5 % and the average method recovery was in the range of 93.4 %-107.5%. The plasma concentration-time curves indicated that tmax was delayed after administration of progesterone-loaded lipid nanoparticles, and the bioavailability was increased significantly, compared with contrast solution.

CONCLUSIONThe method developed is stable, simple, rapid, accurate, sensitive and applicable for determining plasma concentrations of progesterone of progesterone-loaded lipid nanoparticles in pharmacokinetic studies.

Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; methods ; Drug Compounding ; Lipids ; chemistry ; Male ; Nanoparticles ; Progesterone ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley