Babalola C P, Bolaji O O, Ogunbona F A, Ezeomah E
Department of Pharmaceutical Chemistry, University of Ibadan, Ibadan, Nigeria.
Afr J Med Med Sci. 2004 Sep;33(3):185-9.
This study compared the absolute bioavailability of quinine sulphate as capsule and as tablet against the intravenous (i.v.) infusion of the drug in twelve male volunteers. Six of the volunteers received intravenous infusion over 4 h as well as the capsule formulation of the drug in a cross-over manner, while the other six received the tablet formulation. Blood samples were taken at predetermined time intervals and plasma analysed for quinine (QN) using reversed-phase HPLC method. QN was rapidly absorbed after the two oral formulations with average t(max) of 2.67 h for both capsule and tablet. The mean elimination half-life of QN from the i.v. and oral dosage forms varied between 10 and 13.5 hr and were not statistically different (P > 0.05). On the contrary, the maximum plasma concentration (C(max)) and area under the curve (AUC) from capsule were comparable to those from i.v. (P > 0.05), while these values were markedly higher than values from tablet formulation (P < 0.05). The therapeutic QN plasma levels were not achieved with the tablet formulation. The absolute bioavailability (F) were 73% (C.l., 53.3 - 92.4%) and 39 % (C.I., 21.7 - 56.6%) for the capsule and tablet respectively and the difference was significant (P < 0.05). The subtherapeutic levels obtained from the tablet form used in this study may cause treatment failure during malaria and caution should be taken when predictions are made from results obtained from different formulations of QN.
本研究比较了硫酸奎宁胶囊和片剂相对于静脉输注该药物在12名男性志愿者中的绝对生物利用度。6名志愿者以交叉方式接受了4小时的静脉输注以及该药物的胶囊制剂,而另外6名志愿者接受了片剂制剂。在预定的时间间隔采集血样,并使用反相高效液相色谱法分析血浆中的奎宁(QN)。两种口服制剂后QN均迅速吸收,胶囊和片剂的平均达峰时间(t(max))均为2.67小时。静脉注射和口服剂型的QN平均消除半衰期在10至13.5小时之间,无统计学差异(P>0.05)。相反,胶囊的最大血浆浓度(C(max))和曲线下面积(AUC)与静脉注射相当(P>0.05),而这些值明显高于片剂制剂的值(P<0.05)。片剂制剂未达到治疗性QN血浆水平。胶囊和片剂的绝对生物利用度(F)分别为73%(可信区间,53.3 - 92.4%)和39%(可信区间,21.7 - 56.6%),差异有统计学意义(P<0.05)。本研究中使用的片剂形式获得的亚治疗水平可能导致疟疾治疗失败,在根据不同QN制剂的结果进行预测时应谨慎。