盐酸纳洛酮舌下含片在犬体内的药代动力学及绝对生物利用度

本文采用高效液相色谱－电化学检测法研究了盐酸纳洛酮舌下含片在犬体内的药代动力学及绝对生物利用度。雄性犬８只，ｉｖ５ｍｇ盐酸纳洛酮后，血浆药物浓度的经时过程符合二室开放模型，分布半衰期（ｔ１／２α）为１２．０ｍｉｎ，消除半衰期（ｔ１／２β）为１４３．４ｍｉｎ，ＡＵＣ为７．９２ｍｇ（ｍｉｎ／Ｌ。犬给予５ｍｇ盐酸纳洛酮舌下含片后，血浆药物浓度的经时过程符合一级吸收二室开放模型，吸收较快，吸收半衰期（ｔ１／２Ｋａ）为１１．０ｍｉｎ，分布半衰期（ｔ１／２α）为１５．４ｍｉｎ，消除半衰期（ｔ１／２β）为１６４．１ｍｉｎ，达峰时间（Ｔｍａｘ）为２７．７ｍｉｎ，高峰浓度（Ｃｍａｘ）为３４．２ｎｇ／ｍｌ，ＡＵＣ为６．７９ｍｇ．ｍｉｎ／Ｌ，盐酸纳洛酮舌下含片的绝对生物利用度为８６．８（１０．９％。经统计学检验，两种途径给药后的ｔ１／２α、ｔ１／２β、（和（均无显著性差异（Ｐ＞０．０５）。上述结果表明，盐酸纳洛酮舌下含片在犬体内的处置过程与ｉｖ途径是相似的，生物利用度较高，预计在临床能产生较好的疗效

Pharmacokinetics and Absolute Bioavailability of the Sublingual Naloxone Hydrochloride Tablet in Dogs

The pharmacokinetics and absolute bioavailability of the sublingual naloxone tablet were studied with HPLC-electrochemical detection. Eight male dogs received single 5 mg dose of naloxone intravenously, the plasma concentration-time curves could be fitted to two-compartment open model, with 12.0 min of t1/2( , 143.4 min of t1/2( and 7.92 mg(min/L of AUC. The same eight dogs received 5 mg dose of the sublingual naloxone tablet after an interval of a week. The main pharmacokinetic parameters were: t1/2ka = 11.0 min, t1/2( = 15.4 min, t1/2( = 164.1 min, Tmax = 27.7 min, Cmax = 34.2 ng / ml, and AUC = 6.79 mg(min / L, respectively. The plasma concentration-time curves were fitted to the first order absorption two-compartment open model also. The mean absolute bioavailability of the sublingual naloxone tablet was 86.8 ( 10.9%. No statistically significant differences were found with t1/2(, t1/2(, ( and ( between the two routes of administration. These results indicated that the course of disposition for naloxone in dogs was similar for the two routes of administration, and the absolute bioavailability of the sublingual naloxone tablet was high. Thus satisfactory clinical effects could be expected.