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Antimicrobial Agents and Chemotherapy, November 1999, p. 2586-2591, Vol. 43, No. 11
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

Mark Mirochnick,1,* Ellen Cooper,1 Ken McIntosh,2 Jing Xu,3 Jane Lindsey,3 David Jacobus,4 Lynne Mofenson, John L. Sullivan,6 Wayne Dankner,7 Lisa M. Frenkel,8 Sharon Nachman,9 Diane W. Wara,10 Daniel Johnson,11 Vincent R. Bonagura,12 Mobeen H. Rathore,13 Coleen K. Cunningham,14 and James McNamara15

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.


* 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.


Antimicrobial Agents and Chemotherapy, November 1999, p. 2586-2591, Vol. 43, No. 11
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.