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Antimicrobial Agents and Chemotherapy, June 1998, p. 1315-1318, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Phase I Safety and Pharmacokinetics Study of Micronized Atovaquone in Human Immunodeficiency Virus-Infected Infants and Children

Walter Hughes,1,* Alejandro Dorenbaum,2 Ram Yogev,3 Belinda Beauchamp,4 Jing Xu,5 James McNamara,6 John Moye,7 Lynette Purdue,6 Russell van Dyke,8 Michael Rogers,9 Brian Sadler,9 and The Pediatric Aids Clinical Trials Group10

St. Jude Children's Research Hospital, Memphis, Tennessee1; University of California, San Francisco, California2; Chicago Children's Memorial Hospital, Chicago, Illinois3; University of Puerto Rico, San Juan, Puerto Rico4; Harvard Medical School, Boston, Massachusetts5; National Institute of Allergy and Infectious Disease6 and National Institute of Child Health and Human Development,7 Bethesda, Maryland; Tulane University School of Medicine, New Orleans, Louisiana8; Glaxo-Wellcome, Research Triangle Park, North Carolina9; and the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland10

Received 7 July 1997/Returned for modification 7 December 1997/Accepted 20 March 1998

A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 µg/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 µg/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day.

* Corresponding author. Mailing address: St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105. Phone: (901) 495-3485. Fax: (901) 522-6616. E-mail: walter.hughes{at}stjude.org.

Antimicrobial Agents and Chemotherapy, June 1998, p. 1315-1318, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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