Pharmacokinetics of ethambutol in children and adults with tuberculosis.
METHODS
Five hospitals in the United States.


OBJECTIVE
To describe ethambutol pharmacokinetics in children and adults with active tuberculosis (TB).


METHODS
Prospective, open-labeled study in 56 adults and 14 children with active tuberculosis who received ethambutol as part of their multidrug TB regimens.


RESULTS
Most serum samples were collected up to 10 h post dose and assayed using a validated gas chromatography assay with mass selective detection (GC/MS). Concentration data were analyzed using non-compartmental and population pharmacokinetic methods. Drug exposure increased with dose, but less than proportionally at doses >3000 mg. Lower than expected maximum serum concentrations (Cmax <2 microg/ml) were common in adults. Very low Cmax (<1 microg/ml) were common in children, as was delayed absorption (time to Cmax >3 h). Many Cmax were at or below typical TB minimal inhibitory concentrations. Cmax values for HIV-positive patients were 20% lower than HIV-negative patients with daily doses, but were similar with larger twice-weekly doses.


CONCLUSIONS
Adult TB patients often had lower than expected ethambutol serum concentrations, and most pediatric TB patients had very low ethambutol serum concentrations. Higher doses and therapeutic drug monitoring may be indicated for many of these patients.
Zhu
M
M
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Burman
W J
WJ
Starke
J R
JR
Stambaugh
J J
JJ
Steiner
P
P
Bulpitt
A E
AE
Ashkin
D
D
Auclair
B
B
Berning
S E
SE
Jelliffe
R W
RW
Jaresko
G S
GS
Peloquin
C A
CA
D000042:Absorption; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004977:Ethambutol / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D014481:United States; D055815:Young Adult
D000995:Antitubercular Agents; D004977:Ethambutol