Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children.
Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0. 3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age.
Mirochnick
M
M
Boston Medical Center, Boston, Massachusetts, USA. markm@bu.edu
Cooper
E
E
McIntosh
K
K
Xu
J
J
Lindsey
J
J
Jacobus
D
D
Mofenson
L
L
Sullivan
J L
JL
Dankner
W
W
Frenkel
L M
LM
Nachman
S
S
Wara
D W
DW
Johnson
D
D
Bonagura
V R
VR
Rathore
M H
MH
Cunningham
C K
CK
McNamara
J
J
D000293:Adolescent; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003622:Dapsone / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control
D000890:Anti-Infective Agents; D003622:Dapsone