Ethambutol in paediatric tuberculosis: aspects of ethambutol serum concentration, efficacy and toxicity in children

• Published in: The international journal of tuberculosis and lung disease Vol. 11; no. 9; pp. 965 - 971
• Main Authors: THEE, S, DETJEN, A, QUARCOO, D, WAHN, U, MAGDORF, K
• Format: Journal Article
• Language: English
• Published: Paris, France IUATLD 01-09-2007; Union internationale contre la tuberculose et les maladies respiratoires
• Subjects: Administration, Oral; Adolescent; Adult; Age Factors; Anti-Tuberculosis Agents; Antitubercular Agents - administration & dosage; Antitubercular Agents - adverse effects; Antitubercular Agents - blood; Biological and medical sciences; Child; Child, Preschool; Children; Dose-Response Relationship, Drug; Drug Therapy Pharmacokinetics; Drug Therapy, Combination; Ethambutol; Ethambutol - administration & dosage; Ethambutol - adverse effects; Ethambutol - blood; Eye Diseases - chemically induced; Female; General aspects; Humans; Male; Medical sciences; Microbial Sensitivity Tests; Miscellaneous; Mycobacterium; Pneumology; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Recurrence; Retrospective Studies; Rifampin - administration & dosage; Tuberculosis - blood; Tuberculosis - drug therapy; Human; Toxicity; Mycobacterial infection; Concentration; drug therapy pharmacokinetics; Infection; anti-tuberculosis agents; Chemotherapy; Treatment; Tuberculosis; children; Bacteriosis; Ethambutol; Serum; Antituberculous agent; Antibacterial agent; Pharmacokinetics; Child; Pneumology
• ISSN: 1027-3719; 1815-7920

SETTING: Ethambutol (EMB) is used as a fourth drug in paediatric anti-tuberculosis treatment. In current recommendations the dosage of EMB is calculated per kg body weight.OBJECTIVE: To present two studies investigating an appropriate EMB dosage in children, and observational data
on its toxicity and efficacy.DESIGN: EMB serum levels in children of different age groups were determined after single oral administration of EMB alone as well as after EMB combined with rifampicin, and optimal dosages were established. The efficacy and toxicity of these EMB dosages were
examined retrospectively.RESULTS: EMB serum levels were lower than those expected in adults receiving a similar oral dose, due to different pharmacokinetics and pharmacodynamics in childhood. Thereafter, children were treated with EMB doses calculated by body surface (867mg/m2).
Ocular toxicity occurred in 0.7% of cases and relapses in 0.8%.CONCLUSION: Current recommended EMB dosages in childhood tuberculosis lead to subtherapeutic serum levels. It appears to be more valid to calculate the EMB dosage on the basis of body surface rather than body weight, leading
to higher dosages especially in younger children. With these dosages, therapeutic serum levels are reached in all age groups, leading to a high efficacy of anti-tuberculosis treatment without increased ocular toxicity.