Akhtamova Z M, Kholodov L E, Dorokhov V V, Gurtovoĭ B L
Antibiot Med Biotekhnol. 1985 Mar;30(3):228-32.
The pharmacokinetics of ampicillin was studied in 38 patients with acute pyelonephritis in the second and third trimesters of pregnancy after the first and the last (28th-32nd) intramuscular injections of the antibiotic. The ampicillin levels in the blood and urine were determined with the agar diffusion method. The pharmacokinetic parameters were estimated in a one-compartmental model by computer The ampicillin levels in the blood and urine of the patients did not practically differ at all the investigation periods (0.5-6 hours after the antibiotic administration) in the second and third trimesters of pregnancy. During the treatment, the rate of ampicillin elimination from the host increased and the period of half-elimination from the blood decreased. The antibiotic levels in the urine within 4-6 hours after the last injection were practically lower in the second trimester of pregnancy as compared with the second trimester. The therapy resulted in an increase in the antibiotic renal clearance, which returned to normal in the second trimester of pregnancy and remained under normal in the third trimester of pregnancy. The increase was due to an approximately 2-fold acceleration of the rate of ampicillin secretion by the renal tubules. The total clearance of ampicillin practically increased in the second trimester of pregnancy and remained decreased in the third trimester of pregnancy. The estimation performed in accordance with the Krueger-Timmer principles on the basis of the characteristic features of the pharmacokinetics of ampicillin shown in the study provides recommendation of the following scheme for pyelonephritis treatment in pregnant women: 500 mg of ampicillin injected intramuscularly every 6 hours followed by gradual decreasing of the intervals between the injections to 4 hours as the rate of ampicillin elimination increases.
对38例妊娠中晚期急性肾盂肾炎患者在首次及末次(第28 - 32周)肌肉注射抗生素后,研究了氨苄西林的药代动力学。采用琼脂扩散法测定血液和尿液中的氨苄西林水平。通过计算机在一室模型中估算药代动力学参数。在妊娠中晚期的所有研究时间段(抗生素给药后0.5 - 6小时),患者血液和尿液中的氨苄西林水平实际上没有差异。治疗期间,宿主对氨苄西林的消除速率增加,血液中半衰期缩短。与孕中期相比,妊娠晚期最后一次注射后4 - 6小时尿液中的抗生素水平实际上较低。治疗导致抗生素肾清除率增加,在妊娠中期恢复正常,在妊娠晚期仍低于正常水平。这种增加是由于肾小管分泌氨苄西林的速率加快了约2倍。氨苄西林的总清除率在妊娠中期实际上增加,在妊娠晚期仍降低。根据本研究中显示的氨苄西林药代动力学特征,按照克鲁格 - 蒂默原理进行的估算为孕妇肾盂肾炎治疗提供了以下方案建议:每6小时肌肉注射500毫克氨苄西林,随后随着氨苄西林消除速率增加,逐渐将注射间隔缩短至4小时。