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Antimicrobial Agents and Chemotherapy, November 1999, p. 2586-2591, Vol. 43, No. 11
Boston Medical Center,1
Children's Hospital,2 and
Harvard School of Public Health,3
Boston, Massachusetts; Jacobus Pharmaceutical Company, Inc.,
Princeton, New Jersey4; National
Institute of Child Health and Human Development, and Division of
AIDS, National Institute of Allergy and Infectious
Diseases,15 Bethesda, Maryland;
University of Massachusetts Medical School, Worcester,
Massachusetts6; University of California
San Diego, San Diego, California7;
Children's Hospital and Medical Center, Seattle,
Washington8; State University of New
York Health Science Center at Stony Brook, Stony Brook, New
York9; University of California San
Francisco, San Francisco, California10;
University of Chicago Children's Hospital, Chicago,
Illinois11; Schneider Children's
Hospital, Long Island Jewish Medical Center, New Hyde Park, New
York12; State University of New
York Health Sciences Center at Syracuse, Syracuse, New
York14; and University of Florida
Health Sciences Center, Jacksonville, Florida13
Received 17 December 1998/Returned for modification 14 March
1999/Accepted 15 July 1999
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.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Pharmacokinetics of Dapsone Administered Daily and
Weekly in Human Immunodeficiency Virus-Infected Children
*
Corresponding author. Mailing address: Boston Medical
Center-Maternity 6, One Boston Medical Center Place, Boston, MA 02118. Phone: (617) 414-5461. Fax: (617) 414-7297. E-mail:
markm{at}bu.edu.
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