A Study On The Pharmacokinetics Of THAMPGF₂ Alpha In Dairy Cows And Its Effect On Persistent Corpus

Prostaglandin F_2? Tromethamine, belonging to the II new imported drugs, which is salt formed by natural PGF_2? and Tromethamine. Our study focus on its` Pharmacokinetics and pharmacodynamics in cows.Purpose: To research the pharmacokinetic characteristics and clinical safety and efficacy of THAMPGF_2? in cows, for example absorption, distribution and elimination et al. To provide a scientific basis for the guidance of clinical safety and effective using drugs.Methods:?1? Pharmacokinetics: Blood concentration of PGF_2? was determined by ELISA. Time-concentration curve was counted by method of residual.?2? Safety pharmacology experiment: Physiological indexes, biochemical indexes and hematological indexes were detected by the analysis of biochemical analyzer or Automatic blood cell analyzer during the treatment. The irritation test was carried on through the muscle stimulation test. Changes at the injection site were detected.?3? Clinical trial: The treated cows were diagnosed by rectal examination, B ultrasound diagnosis, plasma progesterone content detection. The drug group was divided into three groups according to the dosage. The control drug group was injected with 5 mL THAMPGF_2? injection produced by the Pfizer Inc. The control group was injected 5 mL normal saline. Criteria for evaluating therapeutic effect: Cows return to normal heat or diameter of the corpus luteum becomes smaller and disappear.Results:?1? Pharmacokinetics: The kinetics of prostaglandin F_2? tromethamine was fitted to one compartment model with first order. The main parameters of the high, medium and low groups were as follows:Ka 18.22±2.17 h-1, 15.30±0.64 h-1, 20.09±5.03 h-1; t1/2Ka 0.04±0.004 h, 0.05±0.002 h, 0.04±0.01 h; Ke 1.32±0.14 h-1, 1.27±0.12 h-1, 1.40±0.16 h-1; t1/2Ke 0.53±0.06 h, 0.55±0.05 h, 0.50±0.06 h; tmax 0.17 h; Cmax 6.34±0.59 ng/mL, 5.94±0.27 ng/mL, 4.81±0.16 ng/mL; AUC0^t 14.40±2.19 ng·mL-1·h?10.14±1.07 ng·mL-1·h?13.15±4.34 ng·mL-1·h.?2? Safety pharmacology experiment: Physiological indexes, biochemical indexes and hematological indexes were normal in the three drug groups after treatment. There were nothing visible bleeding or swelling in the injected position.?3? Clinical trial: All the cows in the high dose group and mid dose group return to normal heat. Persistent corpus luteum and concentration of P4 return to the normal level.Conclusion: After treated with the prostaglandin F_2? tromethamine, concentration of the serum reached the Cmax at 10 min, and recovered at 100 min, and the physiological indexes, biochemical indexes and hematological indexes were normal. According to the concentration-time data and clinical pharmacodynamics test, it is proposed that the single dose IM injection should be 5 mL?25 mg?.