Weber M W, Gatchalian S R, Ogunlesi O, Smith A, McCracken G H, Qazi S, Weber A F, Olsen K, Mulholland E K
Medical Research Council Laboratories, Fajara, The Gambia.
Pediatr Infect Dis J. 1999 Oct;18(10):896-901. doi: 10.1097/00006454-199910000-00012.
The broad antimicrobial spectrum and affordable price of chloramphenicol make it an attractive first line treatment option for children with severe illnesses in developing countries. Little is known, however, about its pharmacokinetics in young infants in these settings.
We studied infants younger than 3 months of age hospitalized in Manila, Philippines and The Gambia with possible severe bacterial infections likely to benefit from treatment with chloramphenicol. Infants in the first week of life received intramuscular doses of 25 mg/kg chloramphenicol once daily, twice daily in the second through fourth week of life and three times daily from 5 to 12 weeks of age. Blood samples were taken at 0.5, 1, 2 and 3 h after the first dose, 1 h before the second dose and before the repetition doses on subsequent days. In the Philippines a second group of infants was treated with oral chloramphenicol according to the same dosage schedule.
Thirty-eight infants received intramuscular chloramphenicol, and 20 received oral drug. Intramuscular administration resulted in therapeutic concentrations (10 to 25 microg/ml) in 73 to 86% of children in each of the three age groups in the first 6 h and in 50 to 80% on Days 2 and 3. Between 33 and 38% of children had potentially toxic values on Days 2 and 3. In contrast, after oral administration, only about one-half of the children reached therapeutic values in serum at any time up to Day 3 after start of treatment.
Intramuscular chloramphenicol can be used as a second line drug for the treatment of severe infections in infants younger than 90 days of age, where third generation cephalosporins are not available. It quickly achieves therapeutic values in a high proportion of children. However, severe infections should not be treated with oral chloramphenicol in this age group, because therapeutic serum concentrations were inconsistently achieved.
氯霉素抗菌谱广且价格低廉，这使其成为发展中国家重症患儿颇具吸引力的一线治疗选择。然而，在这些地区，关于其在小婴儿体内的药代动力学情况却知之甚少。
我们对在菲律宾马尼拉和冈比亚住院的3个月以下可能患有严重细菌感染且可能从氯霉素治疗中获益的婴儿进行了研究。出生第一周的婴儿每日肌内注射25mg/kg氯霉素一次，第二至四周每日两次，5至12周龄每日三次。在首剂后0.5、1、2和3小时、第二剂前1小时以及后续几天重复给药前采集血样。在菲律宾，另一组婴儿按照相同的给药方案口服氯霉素。
38名婴儿接受了肌内注射氯霉素，20名接受了口服药物。肌内注射给药后，在前6小时，三个年龄组中各有73%至86%的儿童达到治疗浓度（10至25μg/ml），在第2天和第3天为50%至80%。在第2天和第3天，33%至38%的儿童有潜在的中毒值。相比之下，口服给药后，在治疗开始至第3天的任何时间，只有约一半的儿童血清达到治疗值。
在没有第三代头孢菌素的情况下，肌内注射氯霉素可作为90日龄以下婴儿严重感染的二线药物。它能在很大比例的儿童中迅速达到治疗浓度。然而，该年龄组的严重感染不应采用口服氯霉素治疗，因为血清治疗浓度不稳定。
